13-110615636-C-A

Variant names:

• chr13-110615636-C-A
• rs553877471
• NM_001242882.2:c.35C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001242882.2(NAXD):​c.35C>A​(p.Ala12Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A12V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAXD NM_001242882.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.07).

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.35C>A	p.Ala12Asp	missense	Exon 1 of 10	NP_001229811.1	A0A7P0T9D8
	NAXD	NM_001242883.2		c.45C>A	p.Gly15Gly	synonymous	Exon 1 of 7	NP_001229812.1	Q8IW45-4
	NAXD	NM_018210.4		c.-39C>A		5_prime_UTR	Exon 1 of 10	NP_060680.2	Q8IW45-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAXD	ENST00000680254.1	MANE Select	c.35C>A	p.Ala12Asp	missense	Exon 1 of 10	ENSP00000505619.1	A0A7P0T9D8
	NAXD	ENST00000679389.1		c.35C>A	p.Ala12Asp	missense	Exon 1 of 10	ENSP00000505318.1	A0A7P0T906
	NAXD	ENST00000957157.1		c.35C>A	p.Ala12Asp	missense	Exon 1 of 11	ENSP00000627216.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1338128 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 660778

African (AFR) AF: 0.00 AC: 0 AN: 27566

American (AMR) AF: 0.00 AC: 0 AN: 29152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23552

East Asian (EAS) AF: 0.00 AC: 0 AN: 29360

South Asian (SAS) AF: 0.00 AC: 0 AN: 75162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1057216

Other (OTH) AF: 0.00 AC: 0 AN: 55494

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		-0.094
PromoterAI		-0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=94/6	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs553877471; hg19: chr13-111267983;