chr13-110638697-T-C

Variant names:

• chr13-110638697-T-C
• rs330564
• NM_001242882.2:c.*169T>C

Variant summary

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

The NM_001242882.2(NAXD):​c.*169T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 798,342 control chromosomes in the GnomAD database, including 35,964 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 0.31 (7772 hom., cov: 33)
  • Exomes 𝑓: 0.28 (28192 hom.)
• Consequence: NAXD NM_001242882.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386
• Publications: 13 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):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• NAD(P)HX dehydratase deficiency

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.426 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAXD	NM_001242882.2	MANE Select	c.*169T>C		3_prime_UTR	Exon 10 of 10	NP_001229811.1
	NAXD	NR_040103.1		n.1296T>C		non_coding_transcript_exon	Exon 10 of 10
	NAXD	NR_040104.1		n.1212T>C		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAXD	ENST00000680254.1	MANE Select	c.*169T>C		3_prime_UTR	Exon 10 of 10	ENSP00000505619.1
	NAXD	ENST00000470164.2	TSL:2	n.1081T>C		non_coding_transcript_exon	Exon 9 of 9
	NAXD	ENST00000309957.3	TSL:2	c.*176T>C		3_prime_UTR	Exon 10 of 10	ENSP00000311984.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47781 AN: 151940 Hom.: 7752 Cov.: 33

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.307

GnomAD2 exomes AF: 0.339 AC: 45407 AN: 133850 AF XY: 0.329

Gnomad AFR exome AF: 0.365

Gnomad AMR exome AF: 0.535

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.308

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.269

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.285 AC: 183949 AN: 646284 Hom.: 28192 Cov.: 8 AF XY: 0.284 AC XY: 97995 AN XY: 344450

African (AFR) AF: 0.353 AC: 6141 AN: 17378

American (AMR) AF: 0.517 AC: 18028 AN: 34892

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 6167 AN: 20602

East Asian (EAS) AF: 0.306 AC: 9968 AN: 32580

South Asian (SAS) AF: 0.318 AC: 20378 AN: 64096

European-Finnish (FIN) AF: 0.315 AC: 10508 AN: 33408

Middle Eastern (MID) AF: 0.304 AC: 1306 AN: 4290

European-Non Finnish (NFE) AF: 0.250 AC: 101490 AN: 405270

Other (OTH) AF: 0.295 AC: 9963 AN: 33768

GnomAD4 genome AF: 0.315 AC: 47843 AN: 152058 Hom.: 7772 Cov.: 33 AF XY: 0.319 AC XY: 23727 AN XY: 74318

African (AFR) AF: 0.353 AC: 14640 AN: 41468

American (AMR) AF: 0.435 AC: 6645 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3472

East Asian (EAS) AF: 0.310 AC: 1608 AN: 5182

South Asian (SAS) AF: 0.320 AC: 1542 AN: 4822

European-Finnish (FIN) AF: 0.312 AC: 3291 AN: 10548

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18062 AN: 67970

Other (OTH) AF: 0.307 AC: 648 AN: 2112

Alfa AF: 0.294 Hom.: 9318

Bravo AF: 0.329

Asia WGS AF: 0.298 AC: 1039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.41
PhyloP100		0.39
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: rs330564; hg19: chr13-111291044; COSMIC: COSV57288586; COSMIC: COSV57288586;