Variant 17-58569254-G-A 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_031272.5(TEX14):c.3824C>T(p.Ala1275Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000948 in 1,613,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

TEX14
NM_031272.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

Variant links:

Genes affected

TEX14 (HGNC:11737): (testis expressed 14, intercellular bridge forming factor) The protein encoded by this gene is necessary for intercellular bridges in germ cells, which are required for spermatogenesis. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

TEX14 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=0.014891088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TEX14	NM_031272.5 linkuse as main transcript	c.3824C>T	p.Ala1275Val	missense_variant	26/32	ENST00000349033.10
TEX14	NM_001201457.2 linkuse as main transcript	c.3962C>T	p.Ala1321Val	missense_variant	27/33
TEX14	NM_198393.4 linkuse as main transcript	c.3944C>T	p.Ala1315Val	missense_variant	27/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX14	ENST00000349033.10 linkuse as main transcript	c.3824C>T	p.Ala1275Val	missense_variant	26/32	5	NM_031272.5	A2	Q8IWB6-3

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000207

AC:

AN:

250764

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.0000753

AC:

110

AN:

1461496

Hom.:

Cov.:

AF XY:

0.0000646

AC XY:

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000282

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000374

Hom.:

Bravo

AF:

0.000310

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000594

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

Sep 27, 2021

The c.3944C>T (p.A1315V) alteration is located in exon 27 (coding exon 26) of the TEX14 gene. This alteration results from a C to T substitution at nucleotide position 3944, causing the alanine (A) at amino acid position 1315 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

.;T;.

Eigen

Benign

0.033

Eigen_PC

Benign

0.090

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.5

.;L;.

MutationTaster

Benign

0.97

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.23

Sift

Benign

0.030

D;D;D

Sift4G

Benign

0.13

T;T;D

Polyphen

0.81

P;P;P

Vest4

0.30

MVP

0.87

MPC

0.14

ClinPred

0.081

GERP RS

3.6

Varity_R

0.070

gMVP

0.069

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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