Variant 8-30837140-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001350162.2(TEX15):c.9144G>C(p.Gln3048His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,613,856 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

TEX15
NM_001350162.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.162

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043170124).

BP6

Variant 8-30837140-C-G is Benign according to our data. Variant chr8-30837140-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3176347.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX15	NM_001350162.2 linkuse as main transcript	c.9144G>C	p.Gln3048His	missense_variant	10/11	ENST00000643185.2	NP_001337091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEX15	ENST00000643185.2 linkuse as main transcript	c.9144G>C	p.Gln3048His	missense_variant	10/11		NM_001350162.2	ENSP00000493555.1	A0A2R8Y358
TEX15	ENST00000256246.5 linkuse as main transcript	c.7995G>C	p.Gln2665His	missense_variant	3/4	1		ENSP00000256246.2	Q9BXT5
TEX15	ENST00000638951.1 linkuse as main transcript	c.9156G>C	p.Gln3052His	missense_variant	9/10	5		ENSP00000492713.1	A0A1W2PS94

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000111

AC:

AN:

251228

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000324

AC:

473

AN:

1461766

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

225

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000409

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000171

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000272

Hom.:

Bravo

AF:

0.000159

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.6

DANN

Benign

0.10

DEOGEN2

Benign

0.031

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.29

T;T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

.;N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

2.6

.;N;.

REVEL

Benign

0.076

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

.;T;.

Polyphen

0.0

.;B;.

Vest4

0.13

MutPred

0.34

.;Loss of sheet (P = 0.1501);.;

MVP

0.099

MPC

0.024

ClinPred

0.026

GERP RS

-4.8

Varity_R

0.041

gMVP

0.24

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