NM_000637.5:c.1420-40_1420-38delAAA

Variant names:

• chr8-30679706-CTTT-C
• rs10715710
• NM_000637.5:c.1420-40_1420-38delAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000637.5(GSR):​c.1420-40_1420-38delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00649 in 1,280,356 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0072 (0 hom.)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

Genes affected

GSR (HGNC:4623): (glutathione-disulfide reductase) This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. This enzyme is a homodimeric flavoprotein. It is a central enzyme of cellular antioxidant defense, and reduces oxidized glutathione disulfide (GSSG) to the sulfhydryl form GSH, which is an important cellular antioxidant. Rare mutations in this gene result in hereditary glutathione reductase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSR	NM_000637.5	c.1420-40_1420-38delAAA		intron_variant	Intron 12 of 12	ENST00000221130.11	NP_000628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSR	ENST00000221130.11	c.1420-40_1420-38delAAA		intron_variant	Intron 12 of 12	1	NM_000637.5	ENSP00000221130.5

Frequencies

GnomAD3 genomes AF: 0.000119 AC: 16 AN: 134836 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000540

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000546

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000128

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00746 AC: 981 AN: 131578 Hom.: 0 AF XY: 0.00753 AC XY: 545 AN XY: 72352

Gnomad AFR exome AF: 0.00354

Gnomad AMR exome AF: 0.00625

Gnomad ASJ exome AF: 0.00564

Gnomad EAS exome AF: 0.00613

Gnomad SAS exome AF: 0.00430

Gnomad FIN exome AF: 0.00956

Gnomad NFE exome AF: 0.00954

Gnomad OTH exome AF: 0.00749

GnomAD4 exome AF: 0.00724 AC: 8295 AN: 1145520 Hom.: 0 AF XY: 0.00689 AC XY: 3960 AN XY: 575128

Gnomad4 AFR exome AF: 0.00594

Gnomad4 AMR exome AF: 0.00721

Gnomad4 ASJ exome AF: 0.00668

Gnomad4 EAS exome AF: 0.00687

Gnomad4 SAS exome AF: 0.00286

Gnomad4 FIN exome AF: 0.00817

Gnomad4 NFE exome AF: 0.00762

Gnomad4 OTH exome AF: 0.00765

GnomAD4 genome AF: 0.000119 AC: 16 AN: 134836 Hom.: 0 Cov.: 0 AF XY: 0.000154 AC XY: 10 AN XY: 64896

Gnomad4 AFR AF: 0.0000539

Gnomad4 AMR AF: 0.000152

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000546

Gnomad4 NFE AF: 0.000128

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs10715710; hg19: chr8-30537223;