Variant chr1-178514070-C-T 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_032126.5(TEX35):c.83C>T(p.Pro28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,614,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

TEX35
NM_032126.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.636

Variant links:

Genes affected

TEX35 (HGNC:25366): (testis expressed 35) Located in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

TEX35 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=0.03493032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TEX35	NM_032126.5 linkuse as main transcript	c.83C>T	p.Pro28Leu	missense_variant	2/9	ENST00000319416.7
TEX35	NM_001170722.2 linkuse as main transcript	c.107C>T	p.Pro36Leu	missense_variant	2/9
TEX35	NM_001170723.2 linkuse as main transcript	c.83C>T	p.Pro28Leu	missense_variant	2/9
TEX35	NM_001170724.2 linkuse as main transcript	c.83C>T	p.Pro28Leu	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX35	ENST00000319416.7 linkuse as main transcript	c.83C>T	p.Pro28Leu	missense_variant	2/9	1	NM_032126.5	A2	Q5T0J7-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152200

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:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000139

AC:

AN:

251436

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

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:

0.000246

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000248

AC:

363

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000221

AC XY:

161

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

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:

0.000299

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000190

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000653

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:

0.000181

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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

Jun 18, 2021

The c.83C>T (p.P28L) alteration is located in exon 2 (coding exon 2) of the TEX35 gene. This alteration results from a C to T substitution at nucleotide position 83, causing the proline (P) at amino acid position 28 to be replaced by a leucine (L). 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

0.13

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;.;.;.;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.61

T;T;T;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.035

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.90

L;L;.;L;.

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.1

N;N;D;N;N

REVEL

Benign

0.035

Sift

Benign

1.0

T;T;D;T;T

Sift4G

Benign

1.0

T;T;D;T;T

Polyphen

0.12

B;.;.;B;B

Vest4

0.18

MVP

0.067

MPC

0.082

ClinPred

0.036

GERP RS

0.24

Varity_R

0.034

gMVP

0.014

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