8-30679706-CTTTTTT-CTTTTTTT

Variant names:

• chr8-30679706-C-CT
• rs10715710
• NM_000637.5:c.1420-38dupA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000637.5(GSR):​c.1420-38dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 1 publications found

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]

GSR Gene-Disease associations (from GenCC):

• hemolytic anemia due to glutathione reductase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000637.5. 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
	GSR	NM_000637.5	MANE Select	c.1420-38dupA		intron	N/A	NP_000628.2	P00390-1
	GSR	NM_001195102.3		c.1333-38dupA		intron	N/A	NP_001182031.1	P00390-3
	GSR	NM_001195103.3		c.1261-38dupA		intron	N/A	NP_001182032.1	P00390-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSR	ENST00000221130.11	TSL:1 MANE Select	c.1420-38_1420-37insA		intron	N/A	ENSP00000221130.5	P00390-1
	GSR	ENST00000546342.5	TSL:1	c.1333-38_1333-37insA		intron	N/A	ENSP00000445516.1	P00390-3
	GSR	ENST00000541648.5	TSL:1	c.1261-38_1261-37insA		intron	N/A	ENSP00000444559.1	P00390-4

Frequencies

GnomAD3 genomes AF: 0.00133 AC: 180 AN: 134856 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00340

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00264

Gnomad FIN AF: 0.00382

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000160

Gnomad OTH AF: 0.00164

GnomAD2 exomes AF: 0.00706 AC: 929 AN: 131578 AF XY: 0.00683

Gnomad AFR exome AF: 0.0157

Gnomad AMR exome AF: 0.00580

Gnomad ASJ exome AF: 0.00391

Gnomad EAS exome AF: 0.00241

Gnomad FIN exome AF: 0.00754

Gnomad NFE exome AF: 0.00612

Gnomad OTH exome AF: 0.00663

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0105 AC: 12232 AN: 1162728 Hom.: 0 Cov.: 0 AF XY: 0.0101 AC XY: 5922 AN XY: 583464

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0232 AC: 622 AN: 26764

American (AMR) AF: 0.00573 AC: 193 AN: 33668

Ashkenazi Jewish (ASJ) AF: 0.00582 AC: 127 AN: 21840

East Asian (EAS) AF: 0.00444 AC: 143 AN: 32236

South Asian (SAS) AF: 0.00892 AC: 662 AN: 74230

European-Finnish (FIN) AF: 0.00933 AC: 356 AN: 38144

Middle Eastern (MID) AF: 0.00910 AC: 32 AN: 3516

European-Non Finnish (NFE) AF: 0.0108 AC: 9588 AN: 883724

Other (OTH) AF: 0.0105 AC: 509 AN: 48606

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00133 AC: 179 AN: 134856 Hom.: 0 Cov.: 0 AF XY: 0.00142 AC XY: 92 AN XY: 64910

African (AFR) AF: 0.00337 AC: 125 AN: 37082

American (AMR) AF: 0.000152 AC: 2 AN: 13168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3220

East Asian (EAS) AF: 0.00 AC: 0 AN: 4576

South Asian (SAS) AF: 0.00265 AC: 11 AN: 4146

European-Finnish (FIN) AF: 0.00382 AC: 28 AN: 7334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.000160 AC: 10 AN: 62372

Other (OTH) AF: 0.00163 AC: 3 AN: 1842

Alfa AF: 0.00708 Hom.: 959

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10715710; hg19: chr8-30537223;