Variant X-101269197-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001168474.2(TAF7L):c.1127A>G(p.Lys376Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,208,083 control chromosomes in the GnomAD database, including 1 homozygotes. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 1 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

TAF7L
NM_001168474.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Variant links:

Genes affected

TAF7L (HGNC:11548): (TATA-box binding protein associated factor 7 like) This gene is similar to a mouse gene that encodes a TATA box binding protein-associated factor, and shows testis-specific expression. The encoded protein could be a spermatogenesis-specific component of the DNA-binding general transcription factor complex TFIID. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

TAF7L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF7L	NM_001168474.2 link	c.1127A>G	p.Lys376Arg	missense_variant	13/13	ENST00000356784.2	NP_001161946.1	Q5H9L4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TAF7L	ENST00000356784.2 link	c.1127A>G	p.Lys376Arg	missense_variant	13/13	1	NM_001168474.2	ENSP00000349235.1	Q5H9L4-2
TAF7L	ENST00000372907.7 link	c.1385A>G	p.Lys462Arg	missense_variant	13/13	1		ENSP00000361998.3	Q5H9L4-1
TAF7L	ENST00000324762.10 link	c.905A>G	p.Lys302Arg	missense_variant	11/11	2		ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

112279

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34439

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0247

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1095804

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

361272

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000357

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000151

AC:

AN:

112279

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34439

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000159

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2023

The c.1385A>G (p.K462R) alteration is located in exon 13 (coding exon 13) of the TAF7L gene. This alteration results from a A to G substitution at nucleotide position 1385, causing the lysine (K) at amino acid position 462 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;.

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.55

T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.0

M;.;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.076

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.033

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.16

MutPred

0.23

Loss of methylation at K462 (P = 0.0173);.;.;

MVP

0.22

MPC

0.84

ClinPred

0.90

GERP RS

4.2

Varity_R

0.27

gMVP

0.013

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.26

Position offset: 0

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