chrX-101282375-T-C

Variant names:

• chrX-101282375-T-C
• rs1924443151
• NM_001168474.2:c.358A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001168474.2(TAF7L):​c.358A>G​(p.Arg120Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,097,810 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.000019 (0 hom. 5 hem.)
• Consequence: TAF7L NM_001168474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08515698).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

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.358A>G	p.Arg120Gly	missense	Exon 5 of 13	NP_001161946.1	Q5H9L4-2
	TAF7L	NM_024885.4		c.616A>G	p.Arg206Gly	missense	Exon 5 of 13	NP_079161.3	Q5H9L4-1
	TAF7L	NM_001410720.1		c.358A>G	p.Arg120Gly	missense	Exon 5 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.358A>G	p.Arg120Gly	missense	Exon 5 of 13	ENSP00000349235.1	Q5H9L4-2
	TAF7L	ENST00000372907.7	TSL:1	c.616A>G	p.Arg206Gly	missense	Exon 5 of 13	ENSP00000361998.3	Q5H9L4-1
	TAF7L	ENST00000324762.10	TSL:2	c.358A>G	p.Arg120Gly	missense	Exon 4 of 11	ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.0000191 AC: 21 AN: 1097810 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 5 AN XY: 363170

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35199

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19378

East Asian (EAS) AF: 0.00 AC: 0 AN: 30199

South Asian (SAS) AF: 0.00 AC: 0 AN: 54129

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.0000226 AC: 19 AN: 841788

Other (OTH) AF: 0.0000434 AC: 2 AN: 46073

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

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	0.075
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.81
DEOGEN2	Benign	0.089	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	N
PhyloP100		1.4
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.027
Sift	Benign	0.57	T
Sift4G	Benign	0.39	T
Polyphen		0.0010	B
Vest4		0.066
MutPred		0.35		Loss of MoRF binding (P = 0.0154)
MVP		0.043
MPC		0.34
ClinPred		0.039	T
GERP RS		-2.3
Varity_R		0.080
gMVP		0.11
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1924443151; hg19: chrX-100537363;