5-145859441-A-G

Position:

• chr5-145859441-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080516.2(GRXCR2):​c.*292T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 411,464 control chromosomes in the GnomAD database, including 61,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (20135 hom., cov: 32)
  • Exomes 𝑓: 0.56 (41114 hom.)
• Consequence: GRXCR2 NM_001080516.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.805

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-145859441-A-G is Benign according to our data. Variant chr5-145859441-A-G is described in ClinVar as [Benign]. Clinvar id is 1240861.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRXCR2	NM_001080516.2	c.*292T>C		3_prime_UTR_variant	3/3	ENST00000377976.3	NP_001073985.1
GRXCR2	XM_017009708.2	c.*292T>C		3_prime_UTR_variant	3/3		XP_016865197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRXCR2	ENST00000377976.3	c.*292T>C		3_prime_UTR_variant	3/3	2	NM_001080516.2	ENSP00000367214	P1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76774 AN: 151934 Hom.: 20132 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.557 AC: 144558 AN: 259412 Hom.: 41114 Cov.: 0 AF XY: 0.554 AC XY: 74654 AN XY: 134658

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.550

Gnomad4 ASJ exome AF: 0.591

Gnomad4 EAS exome AF: 0.477

Gnomad4 SAS exome AF: 0.501

Gnomad4 FIN exome AF: 0.606

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.559

GnomAD4 genome AF: 0.505 AC: 76802 AN: 152052 Hom.: 20135 Cov.: 32 AF XY: 0.504 AC XY: 37466 AN XY: 74328

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.518

Alfa AF: 0.557 Hom.: 14681

Bravo AF: 0.492

Asia WGS AF: 0.482 AC: 1675 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs455117; hg19: chr5-145239004;