chr13-110622234-C-T

Variant names:

• chr13-110622234-C-T
• rs373011260
• NM_001242882.2:c.65C>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.65C>T​(p.Ser22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S22S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: NAXD NM_001242882.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11079839).

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.65C>T	p.Ser22Leu	missense	Exon 2 of 10	NP_001229811.1	A0A7P0T9D8
	NAXD	NM_018210.4		c.119C>T	p.Ser40Leu	missense	Exon 2 of 10	NP_060680.2	Q8IW45-2
	NAXD	NM_001242881.2		c.119C>T	p.Ser40Leu	missense	Exon 2 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.65C>T	p.Ser22Leu	missense	Exon 2 of 10	ENSP00000505619.1	A0A7P0T9D8
	NAXD	ENST00000309957.3	TSL:2	c.119C>T	p.Ser40Leu	missense	Exon 2 of 10	ENSP00000311984.2	Q8IW45-2
	NAXD	ENST00000679389.1		c.65C>T	p.Ser22Leu	missense	Exon 2 of 10	ENSP00000505318.1	A0A7P0T906

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152128 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 249786 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000248

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460546 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726494

African (AFR) AF: 0.0000598 AC: 2 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86050

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111370

Other (OTH) AF: 0.0000331 AC: 2 AN: 60350

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152246 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74442

African (AFR) AF: 0.0000722 AC: 3 AN: 41530

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000416

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	0.031
Eigen_PC	Benign	0.045
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.11
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.019	D
Polyphen		0.64	P
Vest4		0.39
MVP		0.57
MPC		0.24
ClinPred		0.65	D
GERP RS		5.0
gMVP		0.74
Mutation Taster		=86/14	polymorphism

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: rs373011260; hg19: chr13-111274581;