chr8-30836916-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001350162.2(TEX15):c.9368C>T(p.Ser3123Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00663 in 1,614,150 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 39 hom. )

Consequence

TEX15
NM_001350162.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.343

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064715445).

BP6

Variant 8-30836916-G-A is Benign according to our data. Variant chr8-30836916-G-A is described in ClinVar as [Benign]. Clinvar id is 770379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00477 (727/152284) while in subpopulation NFE AF= 0.00682 (464/68014). AF 95% confidence interval is 0.00631. There are 7 homozygotes in gnomad4. There are 356 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX15	NM_001350162.2 link	c.9368C>T	p.Ser3123Phe	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.9368C>T	p.Ser3123Phe	missense_variant	Exon 10 of 11		NM_001350162.2	ENSP00000493555.1	A0A2R8Y358
TEX15	ENST00000256246.5 link	c.8219C>T	p.Ser2740Phe	missense_variant	Exon 3 of 4	1		ENSP00000256246.2	Q9BXT5
TEX15	ENST00000638951.1 link	c.9380C>T	p.Ser3127Phe	missense_variant	Exon 9 of 10	5		ENSP00000492713.1	A0A1W2PS94

Frequencies

GnomAD3 genomes

AF:

0.00478

AC:

727

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00682

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00529

AC:

1330

AN:

251364

Hom.:

AF XY:

0.00534

AC XY:

725

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00843

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0141

Gnomad NFE exome

AF:

0.00718

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00682

AC:

9974

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00645

AC XY:

4693

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00761

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.00770

Gnomad4 OTH exome

AF:

0.00575

GnomAD4 genome

AF:

0.00477

AC:

727

AN:

152284

Hom.:

Cov.:

AF XY:

0.00478

AC XY:

356

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.00682

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00680

Hom.:

Bravo

AF:

0.00405

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00469

AC:

569

EpiCase

AF:

0.00649

EpiControl

AF:

0.00533

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

TEX15-related disorder

Benign:1

Jul 12, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.065

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.54

T;T;T

MetaRNN

Benign

0.0065

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;.

PrimateAI

Benign

0.36

PROVEAN

Benign

0.47

.;N;.

REVEL

Benign

0.036

Sift

Benign

0.11

.;T;.

Sift4G

Benign

0.15

.;T;.

Polyphen

0.0

.;B;.

Vest4

0.25

MVP

0.17

MPC

0.025

ClinPred

0.0081

GERP RS

0.079

Varity_R

0.033

gMVP

0.086

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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