8-30837061-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001350162.2(TEX15):c.9223G>A(p.Gly3075Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,614,094 control chromosomes in the GnomAD database, including 9 homozygotes. 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 7 hom. )

Consequence

TEX15
NM_001350162.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.928

Variant links:

Genes affected

TEX15 (HGNC:11738): (testis expressed 15, meiosis and synapsis associated) This gene encodes a protein that is required for DNA double-strand break repair, chromosome synapsis, and meiotic recombination in spermatocytes. Male mice with a knockout of the orthologous gene are viable but sterile. Loss-of-function mutations in the orthologous mouse gene cause early meiotic arrest in spermatocytes, before the mid-pachytene stage. Naturally occurring mutations in this gene are associated with nonobstructive azoospermia. [provided by RefSeq, Apr 2017]

TEX15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00548172).

BP6

Variant 8-30837061-C-T is Benign according to our data. Variant chr8-30837061-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 684768.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00157 (239/152234) while in subpopulation AMR AF= 0.00497 (76/15290). AF 95% confidence interval is 0.00407. There are 2 homozygotes in gnomad4. There are 124 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX15	NM_001350162.2 link	c.9223G>A	p.Gly3075Arg	missense_variant	Exon 10 of 11	ENST00000643185.2	NP_001337091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TEX15	ENST00000643185.2 link	c.9223G>A	p.Gly3075Arg	missense_variant	Exon 10 of 11		NM_001350162.2	ENSP00000493555.1	A0A2R8Y358
TEX15	ENST00000256246.5 link	c.8074G>A	p.Gly2692Arg	missense_variant	Exon 3 of 4	1		ENSP00000256246.2	Q9BXT5
TEX15	ENST00000638951.1 link	c.9235G>A	p.Gly3079Arg	missense_variant	Exon 9 of 10	5		ENSP00000492713.1	A0A1W2PS94

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

239

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00154

AC:

386

AN:

251304

Hom.:

AF XY:

0.00169

AC XY:

230

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00327

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00271

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00152

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00159

AC:

2321

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1194

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00340

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00311

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00162

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152234

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00187

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00153

Hom.:

Bravo

AF:

0.00163

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00142

AC:

172

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00148

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 14, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TEX15: BP4, BS2 -

Non-obstructive azoospermia

Uncertain:1

Jun 07, 2020

Institute of Reproductive Genetics, University of Münster

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

.;T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;L;.

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.6

.;D;.

REVEL

Benign

0.059

Sift

Benign

0.034

.;D;.

Sift4G

Uncertain

0.028

.;D;.

Polyphen

0.98

.;D;.

Vest4

0.39

MutPred

0.27

.;Loss of loop (P = 0.0804);.;

MVP

0.34

MPC

0.19

ClinPred

0.040

GERP RS

3.3

Varity_R

0.13

gMVP

0.19

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