Genetic Variant TAF7L:p.Val175Met (chrX-101278103-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001168474.2(TAF7L):c.523G>A(p.Val175Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000108 in 1,208,678 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V175L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000091 ( 0 hom. 6 hem. )

Consequence

TAF7L
NM_001168474.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.37

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.913

BS2

High Hemizygotes in GnomAdExome4 at 6 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAF7L	NM_001168474.2	MANE Select	c.523G>A	p.Val175Met	missense	Exon 8 of 13	NP_001161946.1	Q5H9L4-2
TAF7L	NM_024885.4		c.781G>A	p.Val261Met	missense	Exon 8 of 13	NP_079161.3	Q5H9L4-1
TAF7L	NM_001410720.1		c.523G>A	p.Val175Met	missense	Exon 8 of 12	NP_001397649.1	Q5H9L4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAF7L	ENST00000356784.2	TSL:1 MANE Select	c.523G>A	p.Val175Met	missense	Exon 8 of 13	ENSP00000349235.1	Q5H9L4-2
TAF7L	ENST00000372907.7	TSL:1	c.781G>A	p.Val261Met	missense	Exon 8 of 13	ENSP00000361998.3	Q5H9L4-1
TAF7L	ENST00000324762.10	TSL:2	c.523G>A	p.Val175Met	missense	Exon 7 of 11	ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

111781

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000950

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183097

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.0000760

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:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000912

AC:

AN:

1096897

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

362273

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26377

American (AMR)

AF:

0.0000284

AC:

AN:

35202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19376

East Asian (EAS)

AF:

0.0000662

AC:

AN:

30190

South Asian (SAS)

AF:

0.00

AC:

AN:

54097

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40465

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00000595

AC:

AN:

841003

Other (OTH)

AF:

0.00

AC:

AN:

46056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000268

AC:

AN:

111781

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33955

show subpopulations

African (AFR)

AF:

0.0000325

AC:

AN:

30750

American (AMR)

AF:

0.0000950

AC:

AN:

10527

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.000280

AC:

AN:

3571

South Asian (SAS)

AF:

0.00

AC:

AN:

2663

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53182

Other (OTH)

AF:

0.00

AC:

AN:

1501

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Uncertain

0.040

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.58

MetaRNN

Pathogenic

0.91

MetaSVM

Benign

-0.48

MutationAssessor

Pathogenic

3.6

PhyloP100

5.4

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.36

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.78

MutPred

0.73

Gain of ubiquitination at K266 (P = 0.0575)

MVP

0.83

MPC

0.94

ClinPred

0.75

GERP RS

4.2

Varity_R

0.39

gMVP

0.69

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over