Variant 5-145859901-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001080516.2(GRXCR2):c.579C>T(p.Pro193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000563 in 1,580,194 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 7 hom. )

Consequence

GRXCR2
NM_001080516.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.586

Variant links:

Genes affected

GRXCR2 (HGNC:33862): (glutaredoxin and cysteine rich domain containing 2) This gene encodes a protein containing a glutaredoxin domain, which functions in protein S-glutathionylation. A mutation in this gene was found in a family with autoosomal recessive nonsyndromic sensorineural deafness-101. [provided by RefSeq, Jun 2014]

GRXCR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 5-145859901-G-A is Benign according to our data. Variant chr5-145859901-G-A is described in ClinVar as [Benign]. Clinvar id is 721108.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.586 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRXCR2	NM_001080516.2 linkuse as main transcript	c.579C>T	p.Pro193=	synonymous_variant	3/3	ENST00000377976.3	NP_001073985.1
GRXCR2	XM_017009708.2 linkuse as main transcript	c.291C>T	p.Pro97=	synonymous_variant	3/3		XP_016865197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRXCR2	ENST00000377976.3 linkuse as main transcript	c.579C>T	p.Pro193=	synonymous_variant	3/3	2	NM_001080516.2	ENSP00000367214	P1
GRXCR2	ENST00000639411.1 linkuse as main transcript	c.174C>T	p.Pro58=	synonymous_variant	4/4	5		ENSP00000491860

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00367

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000865

AC:

193

AN:

223188

Hom.:

AF XY:

0.000900

AC XY:

108

AN XY:

119972

show subpopulations

Gnomad AFR exome

AF:

0.00454

Gnomad AMR exome

AF:

0.000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000397

Gnomad SAS exome

AF:

0.00401

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000389

Gnomad OTH exome

AF:

0.000567

GnomAD4 exome

AF:

0.000479

AC:

684

AN:

1427896

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

378

AN XY:

706812

show subpopulations

Gnomad4 AFR exome

AF:

0.00393

Gnomad4 AMR exome

AF:

0.000176

Gnomad4 ASJ exome

AF:

0.0000419

Gnomad4 EAS exome

AF:

0.00551

Gnomad4 SAS exome

AF:

0.00310

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000183

Gnomad4 OTH exome

AF:

0.00100

GnomAD4 genome

AF:

0.00135

AC:

206

AN:

152298

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00366

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00128

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

GRXCR2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 10, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.4

DANN

Benign

0.85

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