X-101282375-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 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)
  • 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

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 -6 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF7L	NM_001168474.2	c.358A>G	p.Arg120Gly	missense_variant	Exon 5 of 13	ENST00000356784.2	NP_001161946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF7L	ENST00000356784.2	c.358A>G	p.Arg120Gly	missense_variant	Exon 5 of 13	1	NM_001168474.2	ENSP00000349235.1
TAF7L	ENST00000372907.7	c.616A>G	p.Arg206Gly	missense_variant	Exon 5 of 13	1		ENSP00000361998.3
TAF7L	ENST00000324762.10	c.358A>G	p.Arg120Gly	missense_variant	Exon 4 of 11	2		ENSP00000320283.6

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000226

Gnomad4 OTH exome AF: 0.0000434

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.616A>G (p.R206G) 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 616, causing the arginine (R) at amino acid position 206 to be replaced by a glycine (G). 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	0.075
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;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.085	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	N;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.027
Sift	Benign	0.57	T;T;T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.0010	B;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1924443151; hg19: chrX-100537363;