Genetic Variant TAF7L:p.Val348Leu (chrX-101275266-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001168474.2(TAF7L):c.1042G>C(p.Val348Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,164,382 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000012 ( 0 hom. 3 hem. )

Consequence

TAF7L
NM_001168474.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.878

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20049512).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF7L	NM_001168474.2 link	c.1042G>C	p.Val348Leu	missense_variant	Exon 12 of 13	ENST00000356784.2	NP_001161946.1	Q5H9L4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAF7L	ENST00000356784.2 link	c.1042G>C	p.Val348Leu	missense_variant	Exon 12 of 13	1	NM_001168474.2	ENSP00000349235.1	Q5H9L4-2
TAF7L	ENST00000372907.7 link	c.1300G>C	p.Val434Leu	missense_variant	Exon 12 of 13	1		ENSP00000361998.3	Q5H9L4-1
TAF7L	ENST00000324762.10 link	c.820G>C	p.Val274Leu	missense_variant	Exon 10 of 11	2		ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes

AF:

0.0000278

AC:

AN:

107850

Hom.:

Cov.:

AF XY:

0.0000323

AC XY:

AN XY:

30986

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000999

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:

0.00139

GnomAD3 exomes

AF:

0.0000191

AC:

AN:

157212

Hom.:

AF XY:

0.0000201

AC XY:

AN XY:

49682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000914

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000136

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1056532

Hom.:

Cov.:

AF XY:

0.00000907

AC XY:

AN XY:

330642

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000970

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:

0.0000122

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000278

AC:

AN:

107850

Hom.:

Cov.:

AF XY:

0.0000323

AC XY:

AN XY:

30986

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000999

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:

0.00139

Bravo

AF:

0.0000642

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1300G>C (p.V434L) alteration is located in exon 12 (coding exon 12) of the TAF7L gene. This alteration results from a G to C substitution at nucleotide position 1300, causing the valine (V) at amino acid position 434 to be replaced by a leucine (L). 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

0.24

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.2

DANN

Benign

0.96

DEOGEN2

Benign

0.061

T;.;.

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.050

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.38

B;B;.

Vest4

0.16

MutPred

0.15

Loss of MoRF binding (P = 0.2208);.;.;

MVP

0.14

MPC

0.43

ClinPred

0.11

GERP RS

4.3

Varity_R

0.077

gMVP

0.055

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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