Variant 14-75690266-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

TTLL5 (HGNC:):

TTLL5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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/exons	MANE	Protein	UniProt
TTLL5	NM_015072.5 linkuse as main transcript	c.446C>T	p.Ala149Val	missense_variant	6/32	ENST00000298832.14	NP_055887.3	Q6EMB2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL5	ENST00000298832.14 linkuse as main transcript	c.446C>T	p.Ala149Val	missense_variant	6/32	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

GnomAD3 exomes

AF:

0.579

AC:

143584

AN:

248094

Hom.:

44980

AF XY:

0.585

AC XY:

78516

AN XY:

134156

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 SAS exome

AF:

0.524

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

Gnomad4 AFR exome

AF:

0.0938

Gnomad4 AMR exome

AF:

0.627

Gnomad4 ASJ exome

AF:

0.518

Gnomad4 EAS exome

AF:

0.394

Gnomad4 SAS exome

AF:

0.526

Gnomad4 FIN exome

AF:

0.740

Gnomad4 NFE exome

AF:

0.655

Gnomad4 OTH exome

AF:

0.580

GnomAD4 genome

AF:

0.490

AC:

74518

AN:

152050

Hom.:

22666

Cov.:

AF XY:

0.496

AC XY:

36851

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.584

Gnomad4 ASJ

AF:

0.517

Gnomad4 EAS

AF:

0.366

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.752

Gnomad4 NFE

AF:

0.655

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.612

Hom.:

68877

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 26, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cone-rod dystrophy 19

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over