X-101277621-C-T

Position:

• chrX-101277621-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001168474.2(TAF7L):​c.676G>A​(p.Gly226Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: TAF7L NM_001168474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.132

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06737131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF7L	NM_001168474.2	c.676G>A	p.Gly226Ser	missense_variant	9/13	ENST00000356784.2	NP_001161946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF7L	ENST00000356784.2	c.676G>A	p.Gly226Ser	missense_variant	9/13	1	NM_001168474.2	ENSP00000349235.1
TAF7L	ENST00000372907.7	c.934G>A	p.Gly312Ser	missense_variant	9/13	1		ENSP00000361998.3
TAF7L	ENST00000324762.10	c.676G>A	p.Gly226Ser	missense_variant	8/11	2		ENSP00000320283.6

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.934G>A (p.G312S) alteration is located in exon 9 (coding exon 9) of the TAF7L gene. This alteration results from a G to A substitution at nucleotide position 934, causing the glycine (G) at amino acid position 312 to be replaced by a serine (S). 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	0.083
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.72
DEOGEN2	Benign	0.27	T;.;.
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.86	D;T;D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.067	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.3	D;N;D
REVEL	Benign	0.010
Sift	Benign	0.070	T;T;D
Sift4G	Benign	0.24	T;T;T
Polyphen		0.051	B;B;.
Vest4		0.16
MutPred		0.18		Gain of phosphorylation at G312 (P = 0.015);.;.;
MVP		0.082
MPC		0.29
ClinPred		0.038	T
GERP RS		0.95
Varity_R		0.14
gMVP		0.061

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100532609;