chr8-30679706-CTT-C

Variant names:

• chr8-30679701-TTC-TTCTTC
• NM_000637.5:c.1420-37_1420-35dupGAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000637.5(GSR):​c.1420-37_1420-35dupGAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703
• Publications: 0 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 2 ACMG points.

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

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.1420-37_1420-35dupGAA		intron	N/A	NP_000628.2	P00390-1
	GSR	NM_001195102.3		c.1333-37_1333-35dupGAA		intron	N/A	NP_001182031.1	P00390-3
	GSR	NM_001195103.3		c.1261-37_1261-35dupGAA		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.1420-35_1420-34insGAA		intron	N/A	ENSP00000221130.5	P00390-1
	GSR	ENST00000546342.5	TSL:1	c.1333-35_1333-34insGAA		intron	N/A	ENSP00000445516.1	P00390-3
	GSR	ENST00000541648.5	TSL:1	c.1261-35_1261-34insGAA		intron	N/A	ENSP00000444559.1	P00390-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.70

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-30537218;