Genetic Variant TAF7L:p.Glu368Lys (chrX-101269222-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001168474.2(TAF7L):c.1102G>A(p.Glu368Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000597 in 1,206,197 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.000042 ( 0 hom. 15 hem. )

Consequence

TAF7L
NM_001168474.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

Publications

0 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042416096).

BS2

High Hemizygotes in GnomAd4 at 7 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.1102G>A	p.Glu368Lys	missense	Exon 13 of 13	NP_001161946.1	Q5H9L4-2
TAF7L	NM_024885.4		c.1360G>A	p.Glu454Lys	missense	Exon 13 of 13	NP_079161.3	Q5H9L4-1
TAF7L	NM_001410720.1		c.880G>A	p.Glu294Lys	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.1102G>A	p.Glu368Lys	missense	Exon 13 of 13	ENSP00000349235.1	Q5H9L4-2
TAF7L	ENST00000372907.7	TSL:1	c.1360G>A	p.Glu454Lys	missense	Exon 13 of 13	ENSP00000361998.3	Q5H9L4-1
TAF7L	ENST00000324762.10	TSL:2	c.880G>A	p.Glu294Lys	missense	Exon 11 of 11	ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes

AF:

0.000232

AC:

AN:

112017

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000843

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000551

AC:

AN:

181516

AF XY:

0.0000454

show subpopulations

Gnomad AFR exome

AF:

0.000688

Gnomad AMR exome

AF:

0.0000370

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000420

AC:

AN:

1094180

Hom.:

Cov.:

AF XY:

0.0000417

AC XY:

AN XY:

359762

show subpopulations

African (AFR)

AF:

0.00133

AC:

AN:

26353

American (AMR)

AF:

0.0000285

AC:

AN:

35095

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19267

East Asian (EAS)

AF:

0.00

AC:

AN:

30144

South Asian (SAS)

AF:

0.0000188

AC:

AN:

53143

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40397

Middle Eastern (MID)

AF:

0.000485

AC:

AN:

4126

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839726

Other (OTH)

AF:

0.000152

AC:

AN:

45929

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

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:

0.000232

AC:

AN:

112017

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

34199

show subpopulations

African (AFR)

AF:

0.000843

AC:

AN:

30846

American (AMR)

AF:

0.00

AC:

AN:

10498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3578

South Asian (SAS)

AF:

0.00

AC:

AN:

2701

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6109

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53215

Other (OTH)

AF:

0.00

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.000142

Hom.:

Bravo

AF:

0.000268

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

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

0.075

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.8

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.75

M_CAP

Benign

0.022

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

1.1

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.0

REVEL

Benign

0.048

Sift

Benign

0.12

Sift4G

Benign

0.095

Polyphen

0.096

Vest4

0.14

MVP

0.13

MPC

0.31

ClinPred

0.023

GERP RS

1.6

Varity_R

0.086

gMVP

0.042

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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