rs141591089

Variant names:

• chr13-110622229-G-A
• rs141591089
• NM_001242882.2:c.60G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001242882.2(NAXD):​c.60G>A​(p.Ala20Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000772 in 1,612,772 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00079 (7 hom.)
• Consequence: NAXD NM_001242882.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.379
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 13-110622229-G-A is Benign according to our data. Variant chr13-110622229-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1635825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.379 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000644 (98/152270) while in subpopulation SAS AF = 0.00538 (26/4832). AF 95% confidence interval is 0.00377. There are 0 homozygotes in GnomAd4. There are 54 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR,AD gene

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.60G>A	p.Ala20Ala	synonymous	Exon 2 of 10	NP_001229811.1	A0A7P0T9D8
	NAXD	NM_018210.4		c.114G>A	p.Ala38Ala	synonymous	Exon 2 of 10	NP_060680.2	Q8IW45-2
	NAXD	NM_001242881.2		c.114G>A	p.Ala38Ala	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.60G>A	p.Ala20Ala	synonymous	Exon 2 of 10	ENSP00000505619.1	A0A7P0T9D8
	NAXD	ENST00000309957.3	TSL:2	c.114G>A	p.Ala38Ala	synonymous	Exon 2 of 10	ENSP00000311984.2	Q8IW45-2
	NAXD	ENST00000679389.1		c.60G>A	p.Ala20Ala	synonymous	Exon 2 of 10	ENSP00000505318.1	A0A7P0T906

Frequencies

GnomAD3 genomes AF: 0.000644 AC: 98 AN: 152152 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00124 AC: 310 AN: 249534 AF XY: 0.00158

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.000655

Gnomad FIN exome AF: 0.000187

Gnomad NFE exome AF: 0.000868

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000785 AC: 1147 AN: 1460502 Hom.: 7 Cov.: 31 AF XY: 0.000953 AC XY: 692 AN XY: 726454

African (AFR) AF: 0.000209 AC: 7 AN: 33466

American (AMR) AF: 0.00123 AC: 55 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 30 AN: 26100

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39666

South Asian (SAS) AF: 0.00497 AC: 428 AN: 86078

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53172

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5762

European-Non Finnish (NFE) AF: 0.000459 AC: 510 AN: 1111350

Other (OTH) AF: 0.000994 AC: 60 AN: 60346

GnomAD4 genome AF: 0.000644 AC: 98 AN: 152270 Hom.: 0 Cov.: 33 AF XY: 0.000725 AC XY: 54 AN XY: 74446

African (AFR) AF: 0.0000481 AC: 2 AN: 41544

American (AMR) AF: 0.000784 AC: 12 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.00538 AC: 26 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000592 Hom.: 0

Bravo AF: 0.000499

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	NAXD-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.7
DANN	Benign	0.41
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141591089; hg19: chr13-111274576;