NM_001242882.2:c.69A>G

Variant names:

• chr13-110622238-A-G
• rs759721262
• NM_001242882.2:c.69A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001242882.2(NAXD):​c.69A>G​(p.Leu23Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: NAXD NM_001242882.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.234
• 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 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 13-110622238-A-G is Benign according to our data. Variant chr13-110622238-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3029580.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.234 with no splicing effect.

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.69A>G	p.Leu23Leu	synonymous	Exon 2 of 10	NP_001229811.1	A0A7P0T9D8
	NAXD	NM_018210.4		c.123A>G	p.Leu41Leu	synonymous	Exon 2 of 10	NP_060680.2	Q8IW45-2
	NAXD	NM_001242881.2		c.123A>G	p.Leu41Leu	synonymous	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.69A>G	p.Leu23Leu	synonymous	Exon 2 of 10	ENSP00000505619.1	A0A7P0T9D8
	NAXD	ENST00000309957.3	TSL:2	c.123A>G	p.Leu41Leu	synonymous	Exon 2 of 10	ENSP00000311984.2	Q8IW45-2
	NAXD	ENST00000679389.1		c.69A>G	p.Leu23Leu	synonymous	Exon 2 of 10	ENSP00000505318.1	A0A7P0T906

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 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: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250624 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461434 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12 AN XY: 726984

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111806

Other (OTH) AF: 0.0000497 AC: 3 AN: 60386

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NAXD-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.95
DANN	Benign	0.36
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs759721262; hg19: chr13-111274585;