Variant 5-145859800-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080516.2(GRXCR2):c.680A>G(p.Tyr227Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000861 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

GRXCR2
NM_001080516.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.60

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07666883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRXCR2	NM_001080516.2 link	c.680A>G	p.Tyr227Cys	missense_variant	Exon 3 of 3	ENST00000377976.3	NP_001073985.1	A6NFK2
GRXCR2	XM_017009708.2 link	c.392A>G	p.Tyr131Cys	missense_variant	Exon 3 of 3		XP_016865197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRXCR2	ENST00000377976.3 link	c.680A>G	p.Tyr227Cys	missense_variant	Exon 3 of 3	2	NM_001080516.2	ENSP00000367214.1		A6NFK2
GRXCR2	ENST00000639411.1 link	c.275A>G	p.Tyr92Cys	missense_variant	Exon 4 of 4	5		ENSP00000491860.1		A0A1W2PQQ7

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000151

AC:

AN:

251236

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

135764

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:

0.00121

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000848

AC:

124

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.680A>G (p.Y227C) alteration is located in exon 3 (coding exon 3) of the GRXCR2 gene. This alteration results from a A to G substitution at nucleotide position 680, causing the tyrosine (Y) at amino acid position 227 to be replaced by a cysteine (C). 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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

T;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.86

D;D

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.7

D;.

REVEL

Benign

0.20

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.0080

D;.

Polyphen

1.0

D;.

MutPred

0.47

Gain of disorder (P = 0.0128);.;

MVP

0.43

MPC

0.13

ClinPred

0.37

GERP RS

5.6

Varity_R

0.50

gMVP

0.60

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