Variant 14-105411377-C-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_001195082.2(TEX22):c.160C>G(p.Pro54Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000776 in 1,327,966 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000075 ( 1 hom. )

Consequence

TEX22
NM_001195082.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.578

Variant links:

Genes affected

TEX22 (HGNC:40026): (testis expressed 22) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TEX22 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=0.0260458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX22	NM_001195082.2 linkuse as main transcript	c.160C>G	p.Pro54Ala	missense_variant	3/4	ENST00000451127.3	NP_001182011.1
TEX22	XM_006720234.4 linkuse as main transcript	c.160C>G	p.Pro54Ala	missense_variant	3/4		XP_006720297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX22	ENST00000451127.3 linkuse as main transcript	c.160C>G	p.Pro54Ala	missense_variant	3/4	2	NM_001195082.2	ENSP00000397002	P1
TEX22	ENST00000548638.5 linkuse as main transcript	c.150+11887C>G		intron_variant, NMD_transcript_variant		5		ENSP00000449736

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000190

AC:

AN:

31564

Hom.:

AF XY:

0.000211

AC XY:

AN XY:

18916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000177

Gnomad ASJ exome

AF:

0.00133

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000863

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000748

AC:

AN:

1175942

Hom.:

Cov.:

AF XY:

0.0000855

AC XY:

AN XY:

573332

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000699

Gnomad4 ASJ exome

AF:

0.00304

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000258

Gnomad4 OTH exome

AF:

0.000193

GnomAD4 genome

AF:

0.0000987

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000831

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, 2022

The c.160C>G (p.P54A) alteration is located in exon 3 (coding exon 2) of the TEX22 gene. This alteration results from a C to G substitution at nucleotide position 160, causing the proline (P) at amino acid position 54 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

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.12

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-8.0

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.31

Vest4

0.22

MutPred

0.25

Loss of glycosylation at P54 (P = 0.016);

MVP

0.061

ClinPred

0.22

GERP RS

1.8

Varity_R

0.51

gMVP

0.013

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