rs432793

Variant names:

• chr5-145859556-G-C
• rs432793
• NM_001080516.2:c.*177C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080516.2(GRXCR2):​c.*177C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 621,348 control chromosomes in the GnomAD database, including 227,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.88 (59085 hom., cov: 32)
  • Exomes 𝑓: 0.84 (167963 hom.)
• Consequence: GRXCR2 NM_001080516.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.738
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 101

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-145859556-G-C is Benign according to our data. Variant chr5-145859556-G-C is described in ClinVar as Benign. ClinVar VariationId is 1249155.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080516.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRXCR2	NM_001080516.2	MANE Select	c.*177C>G		3_prime_UTR	Exon 3 of 3	NP_001073985.1	A6NFK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRXCR2	ENST00000377976.3	TSL:2 MANE Select	c.*177C>G		3_prime_UTR	Exon 3 of 3	ENSP00000367214.1	A6NFK2
	GRXCR2	ENST00000639411.1	TSL:5	c.*177C>G		3_prime_UTR	Exon 4 of 4	ENSP00000491860.1	A0A1W2PQQ7

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133660 AN: 152126 Hom.: 59026 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.862

GnomAD4 exome AF: 0.845 AC: 396191 AN: 469104 Hom.: 167963 Cov.: 4 AF XY: 0.841 AC XY: 207267 AN XY: 246332

African (AFR) AF: 0.968 AC: 12156 AN: 12554

American (AMR) AF: 0.907 AC: 17404 AN: 19194

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 11999 AN: 13806

East Asian (EAS) AF: 0.964 AC: 29868 AN: 30976

South Asian (SAS) AF: 0.819 AC: 37691 AN: 46046

European-Finnish (FIN) AF: 0.861 AC: 35855 AN: 41628

Middle Eastern (MID) AF: 0.793 AC: 1594 AN: 2010

European-Non Finnish (NFE) AF: 0.821 AC: 227067 AN: 276456

Other (OTH) AF: 0.853 AC: 22557 AN: 26434

GnomAD4 genome AF: 0.879 AC: 133774 AN: 152244 Hom.: 59085 Cov.: 32 AF XY: 0.880 AC XY: 65523 AN XY: 74426

African (AFR) AF: 0.969 AC: 40254 AN: 41560

American (AMR) AF: 0.897 AC: 13723 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3059 AN: 3470

East Asian (EAS) AF: 0.960 AC: 4967 AN: 5172

South Asian (SAS) AF: 0.829 AC: 3996 AN: 4818

European-Finnish (FIN) AF: 0.870 AC: 9227 AN: 10600

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55822 AN: 68012

Other (OTH) AF: 0.860 AC: 1819 AN: 2114

Alfa AF: 0.858 Hom.: 7065

Bravo AF: 0.886

Asia WGS AF: 0.899 AC: 3127 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.53
PhyloP100		-0.74
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs432793; hg19: chr5-145239119;