13-110627655-T-C

Variant names:

• chr13-110627655-T-C
• rs3742193
• NM_001242882.2:c.441+108T>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.441+108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 723,468 control chromosomes in the GnomAD database, including 8,163 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 0.15 (2084 hom., cov: 33)
  • Exomes 𝑓: 0.13 (6079 hom.)
• Consequence: NAXD NM_001242882.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.259 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.441+108T>C		intron	N/A	NP_001229811.1
	NAXD	NM_018210.4		c.495+108T>C		intron	N/A	NP_060680.2
	NAXD	NM_001242881.2		c.495+108T>C		intron	N/A	NP_001229810.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAXD	ENST00000680254.1	MANE Select	c.441+108T>C		intron	N/A	ENSP00000505619.1
	NAXD	ENST00000309957.3	TSL:2	c.495+108T>C		intron	N/A	ENSP00000311984.2
	NAXD	ENST00000679389.1		c.441+108T>C		intron	N/A	ENSP00000505318.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23100 AN: 152122 Hom.: 2059 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.134 AC: 76315 AN: 571230 Hom.: 6079 AF XY: 0.132 AC XY: 39567 AN XY: 300712

African (AFR) AF: 0.177 AC: 2786 AN: 15770

American (AMR) AF: 0.352 AC: 10241 AN: 29122

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 2440 AN: 16382

East Asian (EAS) AF: 0.141 AC: 4592 AN: 32642

South Asian (SAS) AF: 0.126 AC: 6809 AN: 53912

European-Finnish (FIN) AF: 0.103 AC: 4549 AN: 44072

Middle Eastern (MID) AF: 0.115 AC: 333 AN: 2900

European-Non Finnish (NFE) AF: 0.117 AC: 40434 AN: 346372

Other (OTH) AF: 0.137 AC: 4131 AN: 30058

GnomAD4 genome AF: 0.152 AC: 23175 AN: 152238 Hom.: 2084 Cov.: 33 AF XY: 0.154 AC XY: 11454 AN XY: 74438

African (AFR) AF: 0.181 AC: 7526 AN: 41554

American (AMR) AF: 0.266 AC: 4060 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 539 AN: 3470

East Asian (EAS) AF: 0.146 AC: 755 AN: 5174

South Asian (SAS) AF: 0.125 AC: 604 AN: 4826

European-Finnish (FIN) AF: 0.108 AC: 1141 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8155 AN: 67998

Other (OTH) AF: 0.142 AC: 300 AN: 2112

Alfa AF: 0.133 Hom.: 2590

Bravo AF: 0.167

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.79
DANN	Benign	0.37
PhyloP100		-1.3
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)		0.14		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: rs3742193; hg19: chr13-111280002;