rs869320758

Positions:

• chr14-95535168-C-CCGGGCGTG

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_016417.3(GLRX5):​c.86_93dupTGCGGGCG​(p.Ala32fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLRX5 NM_016417.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.330

Genes affected

GLRX5 (HGNC:20134): (glutaredoxin 5) This gene encodes a mitochondrial protein, which is evolutionarily conserved. It is involved in the biogenesis of iron-sulfur clusters, which are required for normal iron homeostasis. Mutations in this gene are associated with autosomal recessive pyridoxine-refractory sideroblastic anemia. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-95535168-C-CCGGGCGTG is Pathogenic according to our data. Variant chr14-95535168-C-CCGGGCGTG is described in ClinVar as [Pathogenic]. Clinvar id is 224513.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRX5	NM_016417.3	c.86_93dupTGCGGGCG	p.Ala32fs	frameshift_variant	1/2	ENST00000331334.5	NP_057501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRX5	ENST00000331334.5	c.86_93dupTGCGGGCG	p.Ala32fs	frameshift_variant	1/2	1	NM_016417.3	ENSP00000328570.4
GLRX5	ENST00000553672.1	n.301+1372_301+1379dupTGCGGGCG		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spasticity-ataxia-gait anomalies syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs869320758; hg19: chr14-96001505;