13-110615636-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001242882.2(NAXD):​c.35C>T​(p.Ala12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,490,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: NAXD NM_001242882.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.055).

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>T	p.Ala12Val	missense	Exon 1 of 10	NP_001229811.1	A0A7P0T9D8
	NAXD	NM_001242883.2		c.45C>T	p.Gly15Gly	synonymous	Exon 1 of 7	NP_001229812.1	Q8IW45-4
	NAXD	NM_018210.4		c.-39C>T		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>T	p.Ala12Val	missense	Exon 1 of 10	ENSP00000505619.1	A0A7P0T9D8
	NAXD	ENST00000679389.1		c.35C>T	p.Ala12Val	missense	Exon 1 of 10	ENSP00000505318.1	A0A7P0T906
	NAXD	ENST00000957157.1		c.35C>T	p.Ala12Val	missense	Exon 1 of 11	ENSP00000627216.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000102 AC: 1 AN: 98352 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000258

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000105 AC: 14 AN: 1338132 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 10 AN XY: 660778

African (AFR) AF: 0.0000363 AC: 1 AN: 27568

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: 35070

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5558

European-Non Finnish (NFE) AF: 0.00000662 AC: 7 AN: 1057216

Other (OTH) AF: 0.0000901 AC: 5 AN: 55494

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152284 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_noAF	Benign	-0.73
CADD	Benign	10
DANN	Benign	0.97
PhyloP100		-0.094
PromoterAI		-0.030	Neutral
Mutation Taster		=92/8	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;