Genetic Variant TAF7L:p.Arg372His (chrX-101269209-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001168474.2(TAF7L):c.1115G>A(p.Arg372His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00884 in 1,207,700 control chromosomes in the GnomAD database, including 41 homozygotes. There are 3,523 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 0.0072 ( 3 hom., 242 hem., cov: 23)

Exomes 𝑓: 0.0090 ( 38 hom. 3281 hem. )

Consequence

TAF7L
NM_001168474.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.483

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002762109).

BP6

Variant X-101269209-C-T is Benign according to our data. Variant chrX-101269209-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1205846.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.009 (9864/1095521) while in subpopulation MID AF = 0.0518 (214/4128). AF 95% confidence interval is 0.0462. There are 38 homozygotes in GnomAdExome4. There are 3281 alleles in the male GnomAdExome4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAF7L	NM_001168474.2	MANE Select	c.1115G>A	p.Arg372His	missense	Exon 13 of 13	NP_001161946.1	Q5H9L4-2
TAF7L	NM_024885.4		c.1373G>A	p.Arg458His	missense	Exon 13 of 13	NP_079161.3	Q5H9L4-1
TAF7L	NM_001410720.1		c.893G>A	p.Arg298His	missense	Exon 12 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.1115G>A	p.Arg372His	missense	Exon 13 of 13	ENSP00000349235.1	Q5H9L4-2
TAF7L	ENST00000372907.7	TSL:1	c.1373G>A	p.Arg458His	missense	Exon 13 of 13	ENSP00000361998.3	Q5H9L4-1
TAF7L	ENST00000324762.10	TSL:2	c.893G>A	p.Arg298His	missense	Exon 11 of 11	ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes

AF:

0.00719

AC:

806

AN:

112129

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0134

Gnomad ASJ

AF:

0.0188

Gnomad EAS

AF:

0.00279

Gnomad SAS

AF:

0.0107

Gnomad FIN

AF:

0.000490

Gnomad MID

AF:

0.0628

Gnomad NFE

AF:

0.00853

Gnomad OTH

AF:

0.0106

GnomAD2 exomes

AF:

0.00641

AC:

1165

AN:

181837

AF XY:

0.00668

show subpopulations

Gnomad AFR exome

AF:

0.00351

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.000437

Gnomad NFE exome

AF:

0.00790

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.00900

AC:

9864

AN:

1095521

Hom.:

Cov.:

AF XY:

0.00909

AC XY:

3281

AN XY:

361087

show subpopulations

African (AFR)

AF:

0.00330

AC:

AN:

26380

American (AMR)

AF:

0.00379

AC:

133

AN:

35135

Ashkenazi Jewish (ASJ)

AF:

0.0166

AC:

320

AN:

19314

East Asian (EAS)

AF:

0.00133

AC:

AN:

30159

South Asian (SAS)

AF:

0.0108

AC:

578

AN:

53491

European-Finnish (FIN)

AF:

0.000791

AC:

AN:

40447

Middle Eastern (MID)

AF:

0.0518

AC:

214

AN:

4128

European-Non Finnish (NFE)

AF:

0.00949

AC:

7979

AN:

840505

Other (OTH)

AF:

0.0105

AC:

481

AN:

45962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

311

622

933

1244

1555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.00724

AC:

812

AN:

112179

Hom.:

Cov.:

AF XY:

0.00704

AC XY:

242

AN XY:

34363

show subpopulations

African (AFR)

AF:

0.00285

AC:

AN:

30929

American (AMR)

AF:

0.0134

AC:

141

AN:

10544

Ashkenazi Jewish (ASJ)

AF:

0.0188

AC:

AN:

2653

East Asian (EAS)

AF:

0.00280

AC:

AN:

3569

South Asian (SAS)

AF:

0.0119

AC:

AN:

2699

European-Finnish (FIN)

AF:

0.000490

AC:

AN:

6120

Middle Eastern (MID)

AF:

0.0691

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00853

AC:

454

AN:

53240

Other (OTH)

AF:

0.0125

AC:

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

109

136

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:

0.00891

Hom.:

478

Bravo

AF:

0.00800

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0111

AC:

ESP6500AA

AF:

0.00417

AC:

ESP6500EA

AF:

0.00847

AC:

ExAC

AF:

0.00679

AC:

824

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.019

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.026

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.48

PrimateAI

Benign

0.23

PROVEAN

Benign

0.41

REVEL

Benign

0.019

Sift

Benign

0.54

Sift4G

Benign

0.57

Polyphen

0.0

Vest4

0.017

MVP

0.082

MPC

0.33

ClinPred

0.00072

GERP RS

-8.7

Varity_R

0.016

gMVP

0.012

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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