X-101282381-T-C

Variant names:

• chrX-101282381-T-C
• rs370305430
• NM_001168474.2:c.352A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001168474.2(TAF7L):​c.352A>G​(p.Ile118Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000405 in 1,208,935 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 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 0.000072 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.000037 (0 hom. 15 hem.)
• Consequence: TAF7L NM_001168474.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.409
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.035093874).
• BP6: Variant X-101282381-T-C is Benign according to our data. Variant chrX-101282381-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3324287.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 2 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.352A>G	p.Ile118Val	missense	Exon 5 of 13	NP_001161946.1	Q5H9L4-2
	TAF7L	NM_024885.4		c.610A>G	p.Ile204Val	missense	Exon 5 of 13	NP_079161.3	Q5H9L4-1
	TAF7L	NM_001410720.1		c.352A>G	p.Ile118Val	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.352A>G	p.Ile118Val	missense	Exon 5 of 13	ENSP00000349235.1	Q5H9L4-2
	TAF7L	ENST00000372907.7	TSL:1	c.610A>G	p.Ile204Val	missense	Exon 5 of 13	ENSP00000361998.3	Q5H9L4-1
	TAF7L	ENST00000324762.10	TSL:2	c.352A>G	p.Ile118Val	missense	Exon 4 of 11	ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes AF: 0.0000717 AC: 8 AN: 111507 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000326

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: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000436 AC: 8 AN: 183467 AF XY: 0.0000442

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000732

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000374 AC: 41 AN: 1097428 Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 15 AN XY: 362784

African (AFR) AF: 0.0000379 AC: 1 AN: 26389

American (AMR) AF: 0.00 AC: 0 AN: 35201

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19377

East Asian (EAS) AF: 0.00 AC: 0 AN: 30195

South Asian (SAS) AF: 0.00 AC: 0 AN: 54124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40508

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

European-Non Finnish (NFE) AF: 0.0000452 AC: 38 AN: 841437

Other (OTH) AF: 0.0000434 AC: 2 AN: 46064

GnomAD4 genome AF: 0.0000717 AC: 8 AN: 111507 Hom.: 0 Cov.: 22 AF XY: 0.0000594 AC XY: 2 AN XY: 33675

African (AFR) AF: 0.0000326 AC: 1 AN: 30650

American (AMR) AF: 0.00 AC: 0 AN: 10444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3564

South Asian (SAS) AF: 0.00 AC: 0 AN: 2641

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6042

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

European-Non Finnish (NFE) AF: 0.000132 AC: 7 AN: 53097

Other (OTH) AF: 0.00 AC: 0 AN: 1497

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000446 AC: 3

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	0.057
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.062
DANN	Benign	0.28
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.70	N
PhyloP100		0.41
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.019
Sift	Benign	1.0	T
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.058
MVP		0.043
MPC		0.22
ClinPred		0.013	T
GERP RS		-0.48
Varity_R		0.032
gMVP		0.069
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs370305430; hg19: chrX-100537369;