X-101278058-C-T

Variant names:

• chrX-101278058-C-T
• rs1924275571
• NM_001168474.2:c.568G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001168474.2(TAF7L):​c.568G>A​(p.Val190Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,207,611 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 3 hem.)
• Consequence: TAF7L NM_001168474.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.479
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.071605116).
• BP6: Variant X-101278058-C-T is Benign according to our data. Variant chrX-101278058-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3324288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 3 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.568G>A	p.Val190Ile	missense	Exon 8 of 13	NP_001161946.1	Q5H9L4-2
	TAF7L	NM_024885.4		c.826G>A	p.Val276Ile	missense	Exon 8 of 13	NP_079161.3	Q5H9L4-1
	TAF7L	NM_001410720.1		c.568G>A	p.Val190Ile	missense	Exon 8 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.568G>A	p.Val190Ile	missense	Exon 8 of 13	ENSP00000349235.1	Q5H9L4-2
	TAF7L	ENST00000372907.7	TSL:1	c.826G>A	p.Val276Ile	missense	Exon 8 of 13	ENSP00000361998.3	Q5H9L4-1
	TAF7L	ENST00000324762.10	TSL:2	c.568G>A	p.Val190Ile	missense	Exon 7 of 11	ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes AF: 0.00000894 AC: 1 AN: 111802 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1095809 Hom.: 0 Cov.: 29 AF XY: 0.00000830 AC XY: 3 AN XY: 361253

African (AFR) AF: 0.0000379 AC: 1 AN: 26356

American (AMR) AF: 0.00 AC: 0 AN: 35195

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19375

East Asian (EAS) AF: 0.00 AC: 0 AN: 30190

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40467

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 839996

Other (OTH) AF: 0.00 AC: 0 AN: 46020

GnomAD4 genome AF: 0.00000894 AC: 1 AN: 111802 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33976

African (AFR) AF: 0.00 AC: 0 AN: 30732

American (AMR) AF: 0.00 AC: 0 AN: 10518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3570

South Asian (SAS) AF: 0.00 AC: 0 AN: 2669

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53204

Other (OTH) AF: 0.00 AC: 0 AN: 1499

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.060
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0010
DANN	Benign	0.78
DEOGEN2	Benign	0.056	T
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.59	N
PhyloP100		-0.48
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.019
Sift	Benign	0.33	T
Sift4G	Benign	0.32	T
Polyphen		0.013	B
Vest4		0.17
MutPred		0.37		Loss of MoRF binding (P = 0.1514)
MVP		0.10
MPC		0.22
ClinPred		0.078	T
GERP RS		-6.7
Varity_R		0.038
gMVP		0.18
Mutation Taster		=100/0	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: rs1924275571; hg19: chrX-100533046; COSMIC: COSV61256291;