Variant 8-30837357-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001350162.2(TEX15):c.8927A>G(p.His2976Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000431 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 0 hom. )

Consequence

TEX15
NM_001350162.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.346

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051359802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX15	NM_001350162.2 linkuse as main transcript	c.8927A>G	p.His2976Arg	missense_variant	10/11	ENST00000643185.2	NP_001337091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TEX15	ENST00000643185.2 linkuse as main transcript	c.8927A>G	p.His2976Arg	missense_variant	10/11		NM_001350162.2	ENSP00000493555	P4
TEX15	ENST00000256246.5 linkuse as main transcript	c.7778A>G	p.His2593Arg	missense_variant	3/4	1		ENSP00000256246
TEX15	ENST00000638951.1 linkuse as main transcript	c.8939A>G	p.His2980Arg	missense_variant	9/10	5		ENSP00000492713	A2

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000647

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000195

AC:

AN:

251164

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000396

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000441

AC:

645

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000411

AC XY:

299

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000567

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000328

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000376

Hom.:

Bravo

AF:

0.000230

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.7778A>G (p.H2593R) alteration is located in exon 3 (coding exon 3) of the TEX15 gene. This alteration results from a A to G substitution at nucleotide position 7778, causing the histidine (H) at amino acid position 2593 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.18

DANN

Benign

0.52

DEOGEN2

Benign

0.032

.;T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.46

T;T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.051

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

.;N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.44

.;N;.

REVEL

Benign

0.032

Sift

Benign

0.34

.;T;.

Sift4G

Benign

0.18

.;T;.

Polyphen

0.60

.;P;.

Vest4

0.19

MVP

0.16

MPC

0.066

ClinPred

0.052

GERP RS

0.23

Varity_R

0.11

gMVP

0.055

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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