Variant chr17-58571941-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.3697C>T(p.Pro1233Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000464 in 1,613,956 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 0.00049 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

TEX14
NM_031272.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

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=0.050789773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TEX14	NM_031272.5 linkuse as main transcript	c.3697C>T	p.Pro1233Ser	missense_variant	24/32	ENST00000349033.10
TEX14	NM_001201457.2 linkuse as main transcript	c.3835C>T	p.Pro1279Ser	missense_variant	25/33
TEX14	NM_198393.4 linkuse as main transcript	c.3817C>T	p.Pro1273Ser	missense_variant	25/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX14	ENST00000349033.10 linkuse as main transcript	c.3697C>T	p.Pro1233Ser	missense_variant	24/32	5	NM_031272.5	A2	Q8IWB6-3

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

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:

0.000661

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000310

AC:

AN:

251394

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000519

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000462

AC:

675

AN:

1461782

Hom.:

Cov.:

AF XY:

0.000437

AC XY:

318

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000547

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000486

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.00239

Alfa

AF:

0.000417

Hom.:

Bravo

AF:

0.000586

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000415

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

Nov 09, 2021

The c.3817C>T (p.P1273S) alteration is located in exon 25 (coding exon 24) of the TEX14 gene. This alteration results from a C to T substitution at nucleotide position 3817, causing the proline (P) at amino acid position 1273 to be replaced by a serine (S). 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

0.083

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.10

DEOGEN2

Benign

0.076

.;T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.051

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.83

.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.011

Sift

Benign

0.064

T;T;T

Sift4G

Benign

0.97

T;T;T

Polyphen

0.010

B;B;B

Vest4

0.17

MVP

0.38

MPC

0.053

ClinPred

0.043

GERP RS

2.7

Varity_R

0.026

gMVP

0.16

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