Genetic Variant TAF7L:p.Val190Ile (chrX-101278058-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

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. 14/20 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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.479

Variant links:

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]

TAF7L links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 3324288.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF7L	NM_001168474.2 link	c.568G>A	p.Val190Ile	missense_variant	Exon 8 of 13	ENST00000356784.2	NP_001161946.1	Q5H9L4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAF7L	ENST00000356784.2 link	c.568G>A	p.Val190Ile	missense_variant	Exon 8 of 13	1	NM_001168474.2	ENSP00000349235.1	Q5H9L4-2
TAF7L	ENST00000372907.7 link	c.826G>A	p.Val276Ile	missense_variant	Exon 8 of 13	1		ENSP00000361998.3	Q5H9L4-1
TAF7L	ENST00000324762.10 link	c.568G>A	p.Val190Ile	missense_variant	Exon 7 of 11	2		ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111802

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33976

show subpopulations

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:

AN:

1095809

Hom.:

Cov.:

AF XY:

0.00000830

AC XY:

AN XY:

361253

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111802

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33976

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 30, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0010

DANN

Benign

0.78

DEOGEN2

Benign

0.056

T;.;.

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.59

N;.;.

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.47

N;N;N

REVEL

Benign

0.019

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.013

B;B;.

Vest4

0.17

MutPred

0.37

Loss of MoRF binding (P = 0.1514);.;.;

MVP

0.10

MPC

0.22

ClinPred

0.078

GERP RS

-6.7

Varity_R

0.038

gMVP

0.18

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over