rs146036604

Positions:

chr14-75783181-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015072.5(TTLL5):c.2637A>C(p.Leu879Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 1,612,776 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 22 hom. )

Consequence

TTLL5
NM_015072.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.868

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:

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=0.003328085).

BP6

Variant 14-75783181-A-C is Benign according to our data. Variant chr14-75783181-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 376879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75783181-A-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00412 (628/152290) while in subpopulation EAS AF= 0.0146 (76/5192). AF 95% confidence interval is 0.012. There are 3 homozygotes in gnomad4. There are 280 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL5	NM_015072.5 linkuse as main transcript	c.2637A>C	p.Leu879Phe	missense_variant	26/32	ENST00000298832.14	NP_055887.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL5	ENST00000298832.14 linkuse as main transcript	c.2637A>C	p.Leu879Phe	missense_variant	26/32	1	NM_015072.5	ENSP00000298832	P4	Q6EMB2-1

Frequencies

GnomAD3 genomes

AF:

0.00413

AC:

628

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0146

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00575

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00472

AC:

1178

AN:

249546

Hom.:

AF XY:

0.00473

AC XY:

639

AN XY:

135090

show subpopulations

Gnomad AFR exome

AF:

0.000751

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.0163

Gnomad SAS exome

AF:

0.00171

Gnomad FIN exome

AF:

0.00119

Gnomad NFE exome

AF:

0.00617

Gnomad OTH exome

AF:

0.00412

GnomAD4 exome

AF:

0.00515

AC:

7523

AN:

1460486

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

3700

AN XY:

726562

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0150

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00561

Gnomad4 OTH exome

AF:

0.00485

GnomAD4 genome

AF:

0.00412

AC:

628

AN:

152290

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

280

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0146

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00575

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00563

Hom.:

Bravo

AF:

0.00421

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00535

AC:

649

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00632

EpiControl

AF:

0.00605

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 03, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 09, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

.;T;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.77

T;T;T;T

MetaRNN

Benign

0.0033

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;L;.;.

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.0

N;N;N;N

REVEL

Benign

0.066

Sift

Benign

0.083

T;T;T;T

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.019

B;B;B;.

Vest4

0.17

MutPred

0.38

Gain of methylation at K892 (P = 0.0332);.;.;.;

MVP

0.19

MPC

0.096

ClinPred

0.0020

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.054

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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