X-101292945-A-T

Position:

• chrX-101292945-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024885.4(TAF7L):​c.101T>A​(p.Leu34His) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L34P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 21)
• Consequence: TAF7L NM_024885.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07214439).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF7L	NM_024885.4	c.101T>A	p.Leu34His	missense_variant	1/13		NP_079161.3
TAF7L	XM_006724664.2	c.101T>A	p.Leu34His	missense_variant	1/13		XP_006724727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF7L	ENST00000372907.7	c.101T>A	p.Leu34His	missense_variant	1/13	1		ENSP00000361998.3

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.72
DEOGEN2	Benign	0.030	T
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.042
Sift	Benign	0.042	D
Sift4G	Benign	0.080	T
Polyphen		0.76	P
Vest4		0.13
MutPred		0.20		Loss of stability (P = 0.1562);
MVP		0.068
MPC		0.40
ClinPred		0.39	T
GERP RS		-2.8
Varity_R		0.064
gMVP		0.15

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

Other links and lift over

dbSNP: rs5951328; hg19: chrX-100547933;