13-110615647-GTT-ATC

Variant names:

• chr13-110615647-GGT-ATC
• NM_001242882.2:c.46_46+2delGGTinsATC
• NAXD p.Val16Ile

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_001242882.2(NAXD):​c.46_46+2delGGTinsATC​(p.Val16Ile) variant causes a splice donor, missense, splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NAXD NM_001242882.2 splice_donor, missense, splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242882.2. 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
	NAXD	NM_001242882.2	MANE Select	c.46_46+2delGGTinsATC	p.Val16Ile	splice_donor missense splice_region intron	N/A	NP_001229811.1	A0A7P0T9D8
	NAXD	NM_018210.4		c.-28_-26delGGTinsATC		5_prime_UTR	Exon 1 of 10	NP_060680.2	Q8IW45-2
	NAXD	NM_001242881.2		c.-28_-26delGGTinsATC		5_prime_UTR	Exon 1 of 10	NP_001229810.1	Q8IW45-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAXD	ENST00000680254.1	MANE Select	c.46_46+2delGGTinsATC	p.Val16Ile	splice_donor missense splice_region intron	N/A	ENSP00000505619.1	A0A7P0T9D8
	NAXD	ENST00000309957.3	TSL:2	c.-28_-26delGGTinsATC		5_prime_UTR	Exon 1 of 10	ENSP00000311984.2	Q8IW45-2
	NAXD	ENST00000680505.1		c.-28_-26delGGTinsATC		5_prime_UTR	Exon 1 of 10	ENSP00000504986.1	Q8IW45-1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

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: chr13-111267994;