chr13-110638533-G-A

Variant names:

• chr13-110638533-G-A
• rs330563
• NM_001242882.2:c.*5G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242882.2(NAXD):​c.*5G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,610,948 control chromosomes in the GnomAD database, including 70,234 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (10127 hom., cov: 33)
  • Exomes 𝑓: 0.28 (60107 hom.)
• Consequence: NAXD NM_001242882.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636
• Publications: 21 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 Gene-Disease associations (from GenCC):

• NAD(P)HX dehydratase deficiency

  Inheritance: AD, AR Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, Baylor College of Medicine Research Center
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

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.*5G>A		3_prime_UTR	Exon 10 of 10	NP_001229811.1	A0A7P0T9D8
	NAXD	NM_018210.4		c.*12G>A		3_prime_UTR	Exon 10 of 10	NP_060680.2	Q8IW45-2
	NAXD	NM_001242881.2		c.*5G>A		3_prime_UTR	Exon 10 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.*5G>A		3_prime_UTR	Exon 10 of 10	ENSP00000505619.1	A0A7P0T9D8
	NAXD	ENST00000309957.3	TSL:2	c.*12G>A		3_prime_UTR	Exon 10 of 10	ENSP00000311984.2	Q8IW45-2
	NAXD	ENST00000679389.1		c.*12G>A		3_prime_UTR	Exon 10 of 10	ENSP00000505318.1	A0A7P0T906

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52991 AN: 151944 Hom.: 10084 Cov.: 33

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.333

GnomAD2 exomes AF: 0.334 AC: 82715 AN: 247394 AF XY: 0.322

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.549

Gnomad ASJ exome AF: 0.312

Gnomad EAS exome AF: 0.310

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.280 AC: 407853 AN: 1458886 Hom.: 60107 Cov.: 34 AF XY: 0.279 AC XY: 202567 AN XY: 725462

African (AFR) AF: 0.495 AC: 16541 AN: 33436

American (AMR) AF: 0.533 AC: 23822 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7860 AN: 26104

East Asian (EAS) AF: 0.307 AC: 12176 AN: 39664

South Asian (SAS) AF: 0.316 AC: 27215 AN: 86194

European-Finnish (FIN) AF: 0.312 AC: 16223 AN: 52076

Middle Eastern (MID) AF: 0.315 AC: 1816 AN: 5756

European-Non Finnish (NFE) AF: 0.256 AC: 284738 AN: 1110674

Other (OTH) AF: 0.290 AC: 17462 AN: 60316

GnomAD4 genome AF: 0.349 AC: 53094 AN: 152062 Hom.: 10127 Cov.: 33 AF XY: 0.353 AC XY: 26205 AN XY: 74322

African (AFR) AF: 0.485 AC: 20124 AN: 41452

American (AMR) AF: 0.444 AC: 6786 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1082 AN: 3472

East Asian (EAS) AF: 0.310 AC: 1600 AN: 5166

South Asian (SAS) AF: 0.314 AC: 1514 AN: 4820

European-Finnish (FIN) AF: 0.309 AC: 3265 AN: 10556

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17691 AN: 68000

Other (OTH) AF: 0.333 AC: 701 AN: 2106

Alfa AF: 0.290 Hom.: 25073

Bravo AF: 0.368

Asia WGS AF: 0.310 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.43
DANN	Benign	0.74
PhyloP100		-0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs330563; hg19: chr13-111290880; COSMIC: COSV57284841; COSMIC: COSV57284841;