13-110615644-CG-C

Position:

• chr13-110615644-CG-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_001242882.2(NAXD):​c.44del​(p.Arg15GlnfsTer3) variant causes a frameshift, splice region 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: NAXD NM_001242882.2 frameshift, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.145

Genes affected

NAXD (HGNC:25576): (NAD(P)HX dehydratase) Enables ATP-dependent NAD(P)H-hydrate dehydratase activity. Predicted to be involved in metabolite repair. Predicted to be located in cytosol; endoplasmic reticulum; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

NAXD-AS1 (HGNC:56341): (NAXD antisense RNA 1)

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-110615644-CG-C is Pathogenic according to our data. Variant chr13-110615644-CG-C is described in ClinVar as [Pathogenic]. Clinvar id is 978059.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAXD	NM_001242882.2	c.44del	p.Arg15GlnfsTer3	frameshift_variant, splice_region_variant	1/10	ENST00000680254.1
NAXD-AS1	NR_182301.1	n.709del		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAXD	ENST00000680254.1	c.44del	p.Arg15GlnfsTer3	frameshift_variant, splice_region_variant	1/10		NM_001242882.2	P2
NAXD-AS1	ENST00000611744.1	n.709del		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

NAD(P)HX dehydratase deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 17, 2020

- -

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: rs1886017689; hg19: chr13-111267991;