14-75690266-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015072.5(TTLL5):c.446C>T(p.Ala149Val) variant causes a missense change. The variant allele was found at a frequency of 0.611 in 1,610,782 control chromosomes in the GnomAD database, including 314,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 22666 hom., cov: 31)

Exomes 𝑓: 0.62 ( 291833 hom. )

Consequence

TTLL5
NM_015072.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.20

Publications

47 publications found

Variant links:

Genes affected

TTLL5 (HGNC:19963): (tubulin tyrosine ligase like 5) This gene encodes a member of the tubulin tyrosine ligase like protein family. This protein interacts with two glucocorticoid receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. This protein may function as a coregulator of glucocorticoid receptor mediated gene induction and repression. This protein may also function as an alpha tubulin polyglutamylase.[provided by RefSeq, Feb 2010]

TTLL5 Gene-Disease associations (from GenCC):

cone-rod dystrophy 19
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
inherited retinal dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TTLL5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.998419E-6).

BP6

Variant 14-75690266-C-T is Benign according to our data. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75690266-C-T is described in CliVar as Benign. Clinvar id is 677189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL5	NM_015072.5 link	c.446C>T	p.Ala149Val	missense_variant	Exon 6 of 32	ENST00000298832.14	NP_055887.3	Q6EMB2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL5	ENST00000298832.14 link	c.446C>T	p.Ala149Val	missense_variant	Exon 6 of 32	1	NM_015072.5	ENSP00000298832.9		Q6EMB2-1

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74521

AN:

151932

Hom.:

22664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.721

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.517

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.521

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.655

Gnomad OTH

AF:

0.514

GnomAD2 exomes

AF:

0.579

AC:

143584

AN:

248094

AF XY:

0.585

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.632

Gnomad ASJ exome

AF:

0.518

Gnomad EAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.742

Gnomad NFE exome

AF:

0.657

Gnomad OTH exome

AF:

0.585

GnomAD4 exome

AF:

0.623

AC:

909252

AN:

1458732

Hom.:

291833

Cov.:

AF XY:

0.622

AC XY:

450958

AN XY:

725496

show subpopulations

African (AFR)

AF:

0.0938

AC:

3136

AN:

33416

American (AMR)

AF:

0.627

AC:

27614

AN:

44066

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

13509

AN:

26094

East Asian (EAS)

AF:

0.394

AC:

15561

AN:

39524

South Asian (SAS)

AF:

0.526

AC:

44961

AN:

85540

European-Finnish (FIN)

AF:

0.740

AC:

39507

AN:

53382

Middle Eastern (MID)

AF:

0.450

AC:

2590

AN:

5756

European-Non Finnish (NFE)

AF:

0.655

AC:

727392

AN:

1110666

Other (OTH)

AF:

0.580

AC:

34982

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

17620

35240

52861

70481

88101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18690

37380

56070

74760

93450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.490

AC:

74518

AN:

152050

Hom.:

22666

Cov.:

AF XY:

0.496

AC XY:

36851

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.122

AC:

5070

AN:

41496

American (AMR)

AF:

0.584

AC:

8928

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

1791

AN:

3464

East Asian (EAS)

AF:

0.366

AC:

1891

AN:

5164

South Asian (SAS)

AF:

0.522

AC:

2512

AN:

4814

European-Finnish (FIN)

AF:

0.752

AC:

7938

AN:

10560

Middle Eastern (MID)

AF:

0.445

AC:

130

AN:

292

European-Non Finnish (NFE)

AF:

0.655

AC:

44527

AN:

67956

Other (OTH)

AF:

0.509

AC:

1075

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1515

3031

4546

6062

7577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.601

Hom.:

90274

Bravo

AF:

0.465

TwinsUK

AF:

0.661

AC:

2452

ALSPAC

AF:

0.652

AC:

2514

ESP6500AA

AF:

0.136

AC:

600

ESP6500EA

AF:

0.651

AC:

5601

ExAC

AF:

0.574

AC:

69700

Asia WGS

AF:

0.424

AC:

1474

AN:

3478

EpiCase

AF:

0.634

EpiControl

AF:

0.631

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cone-rod dystrophy 19

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

.;.;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.97

D;D;D

MetaRNN

Benign

0.0000070

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.77

.;N;N

PhyloP100

5.2

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.97

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.63

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.61

P;B;P

Vest4

0.095

MPC

0.11

ClinPred

0.012

GERP RS

5.3

Varity_R

0.11

gMVP

0.30

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over