X-101282372-T-C

Position:

• chrX-101282372-T-C

Variant summary

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

The NM_001168474.2(TAF7L):​c.361A>G​(p.Lys121Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: TAF7L NM_001168474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88

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=0.10517445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF7L	NM_001168474.2	c.361A>G	p.Lys121Glu	missense_variant	5/13	ENST00000356784.2	NP_001161946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF7L	ENST00000356784.2	c.361A>G	p.Lys121Glu	missense_variant	5/13	1	NM_001168474.2	ENSP00000349235.1
TAF7L	ENST00000372907.7	c.619A>G	p.Lys207Glu	missense_variant	5/13	1		ENSP00000361998.3
TAF7L	ENST00000324762.10	c.361A>G	p.Lys121Glu	missense_variant	4/11	2		ENSP00000320283.6

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

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

Jun 22, 2023

The c.619A>G (p.K207E) alteration is located in exon 5 (coding exon 5) of the TAF7L gene. This alteration results from a A to G substitution at nucleotide position 619, causing the lysine (K) at amino acid position 207 to be replaced by a glutamic acid (E). 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	0.089
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.95
DEOGEN2	Benign	0.14	T;.;.
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.50	T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.021
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.035	B;B;.
Vest4		0.10
MutPred		0.57		Loss of MoRF binding (P = 0.0068);.;.;
MVP		0.082
MPC		0.39
ClinPred		0.073	T
GERP RS		1.8
Varity_R		0.14
gMVP		0.040

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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-100537360;