Genetic Variant TEX11:p.Met156Val (chrX-70853093-T-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_031276.3(TEX11):c.466A>G(p.Met156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,207,138 control chromosomes in the GnomAD database, including 1 homozygotes. There are 111 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., 13 hem., cov: 22)

Exomes 𝑓: 0.00029 ( 1 hom. 98 hem. )

Consequence

TEX11
NM_031276.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:2

Conservation

PhyloP100: -0.243

Publications

15 publications found

Variant links:

Genes affected

TEX11 (HGNC:11733): (testis expressed 11) This gene is X-linked and is expressed in only male germ cells. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TEX11 Gene-Disease associations (from GenCC):

spermatogenic failure, X-linked, 2
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TEX11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007108569).

BP6

Variant X-70853093-T-C is Benign according to our data. Variant chrX-70853093-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 192379.

BS2

High AC in GnomAd4 at 55 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031276.3. 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
	TEX11	NM_031276.3	MANE Select	c.466A>G	p.Met156Val	missense	Exon 7 of 30	NP_112566.2	Q8IYF3-3
	TEX11	NM_001003811.2		c.511A>G	p.Met171Val	missense	Exon 8 of 31	NP_001003811.1	Q8IYF3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TEX11	ENST00000374333.7	TSL:1 MANE Select	c.466A>G	p.Met156Val	missense	Exon 7 of 30	ENSP00000363453.2	Q8IYF3-3
TEX11	ENST00000344304.3	TSL:5	c.511A>G	p.Met171Val	missense	Exon 6 of 29	ENSP00000340995.3	Q8IYF3-1
TEX11	ENST00000395889.6	TSL:2	c.511A>G	p.Met171Val	missense	Exon 8 of 31	ENSP00000379226.2	Q8IYF3-1

Frequencies

GnomAD3 genomes

AF:

0.000495

AC:

AN:

111201

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000967

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00113

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:

0.000440

AC:

AN:

179693

AF XY:

0.000327

show subpopulations

Gnomad AFR exome

AF:

0.00169

Gnomad AMR exome

AF:

0.000331

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00336

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.000287

AC:

315

AN:

1095879

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

AN XY:

361335

show subpopulations

African (AFR)

AF:

0.00201

AC:

AN:

26363

American (AMR)

AF:

0.000342

AC:

AN:

35106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19351

East Asian (EAS)

AF:

0.00799

AC:

241

AN:

30161

South Asian (SAS)

AF:

0.0000186

AC:

AN:

53759

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40465

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

840544

Other (OTH)

AF:

0.000174

AC:

AN:

45998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.000494

AC:

AN:

111259

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

33453

show subpopulations

African (AFR)

AF:

0.00163

AC:

AN:

30671

American (AMR)

AF:

0.0000966

AC:

AN:

10348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00113

AC:

AN:

3525

South Asian (SAS)

AF:

0.00

AC:

AN:

2618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53073

Other (OTH)

AF:

0.00

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000389

Hom.:

Bravo

AF:

0.000718

ESP6500AA

AF:

0.00183

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000437

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

Spermatogenic failure, X-linked, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.95

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0020

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.035

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.28

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.83

PhyloP100

-0.24

PrimateAI

Benign

0.33

PROVEAN

Benign

0.010

REVEL

Benign

0.0080

Sift

Benign

0.57

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.025

MVP

0.043

MPC

0.31

ClinPred

0.0066

GERP RS

-5.8

Varity_R

0.046

gMVP

0.085

Mutation Taster

=100/0

disease causing (ClinVar)

(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