Variant 19-43418320-A-G 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_001130011.3(TEX101):c.673A>G(p.Thr225Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TEX101
NM_001130011.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.297

Variant links:

Genes affected

TEX101 (HGNC:30722): (testis expressed 101) Predicted to be involved in binding activity of sperm to zona pellucida; flagellated sperm motility; and regulation of flagellated sperm motility. Predicted to be located in acrosomal vesicle; extracellular region; and plasma membrane. Predicted to be active in plasma membrane raft. Predicted to be anchored component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TEX101 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=0.048100173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TEX101	NM_001130011.3 linkuse as main transcript	c.673A>G	p.Thr225Ala	missense_variant	6/6	ENST00000598265.2	NP_001123483.1
TEX101	NM_031451.5 linkuse as main transcript	c.727A>G	p.Thr243Ala	missense_variant	9/9		NP_113639.4
TEX101	XM_005259303.4 linkuse as main transcript	c.769A>G	p.Thr257Ala	missense_variant	6/6		XP_005259360.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX101	ENST00000598265.2 linkuse as main transcript	c.673A>G	p.Thr225Ala	missense_variant	6/6	1	NM_001130011.3	ENSP00000472769	P2	Q9BY14-1
TEX101	ENST00000602198.5 linkuse as main transcript	c.727A>G	p.Thr243Ala	missense_variant	8/8	5		ENSP00000472308	A2	Q9BY14-2
TEX101	ENST00000601707.1 linkuse as main transcript	n.777A>G		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251476

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135916

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

May 31, 2022

The c.727A>G (p.T243A) alteration is located in exon 9 (coding exon 6) of the TEX101 gene. This alteration results from a A to G substitution at nucleotide position 727, causing the threonine (T) at amino acid position 243 to be replaced by an alanine (A). 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

0.067

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.9

DANN

Benign

0.49

DEOGEN2

Benign

0.0011

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.25

T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

.;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

Sift4G

Benign

0.38

T;T

Polyphen

0.19

B;B

Vest4

0.092

MutPred

0.29

.;Loss of glycosylation at T225 (P = 0.0132);

MVP

0.055

MPC

0.088

ClinPred

0.023

GERP RS

-5.1

Varity_R

0.026

gMVP

0.31

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