X-101277621-C-T

Variant names:

• chrX-101277621-C-T
• rs1316623308
• NM_001168474.2:c.676G>A

Variant summary

Our verdict is Likely benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G226R) has been classified 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168474.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF7L	NM_001168474.2	MANE Select	c.676G>A	p.Gly226Ser	missense	Exon 9 of 13	NP_001161946.1	Q5H9L4-2
	TAF7L	NM_024885.4		c.934G>A	p.Gly312Ser	missense	Exon 9 of 13	NP_079161.3	Q5H9L4-1
	TAF7L	NM_001410720.1		c.676G>A	p.Gly226Ser	missense	Exon 9 of 12	NP_001397649.1	Q5H9L4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF7L	ENST00000356784.2	TSL:1 MANE Select	c.676G>A	p.Gly226Ser	missense	Exon 9 of 13	ENSP00000349235.1	Q5H9L4-2
	TAF7L	ENST00000372907.7	TSL:1	c.934G>A	p.Gly312Ser	missense	Exon 9 of 13	ENSP00000361998.3	Q5H9L4-1
	TAF7L	ENST00000324762.10	TSL:2	c.676G>A	p.Gly226Ser	missense	Exon 8 of 11	ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 20

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.13
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.010
Sift	Benign	0.070	T
Sift4G	Benign	0.24	T
Polyphen		0.051	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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1316623308; hg19: chrX-100532609;