chr13-110622235-G-T

Variant names:

• chr13-110622235-G-T
• rs150482005
• NM_001242882.2:c.66G>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001242882.2(NAXD):​c.66G>T​(p.Ser22Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,612,230 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: NAXD NM_001242882.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.46
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-110622235-G-T is Benign according to our data. Variant chr13-110622235-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2061243.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.46 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.66G>T	p.Ser22Ser	synonymous	Exon 2 of 10	NP_001229811.1	A0A7P0T9D8
	NAXD	NM_018210.4		c.120G>T	p.Ser40Ser	synonymous	Exon 2 of 10	NP_060680.2	Q8IW45-2
	NAXD	NM_001242881.2		c.120G>T	p.Ser40Ser	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.66G>T	p.Ser22Ser	synonymous	Exon 2 of 10	ENSP00000505619.1	A0A7P0T9D8
	NAXD	ENST00000309957.3	TSL:2	c.120G>T	p.Ser40Ser	synonymous	Exon 2 of 10	ENSP00000311984.2	Q8IW45-2
	NAXD	ENST00000679389.1		c.66G>T	p.Ser22Ser	synonymous	Exon 2 of 10	ENSP00000505318.1	A0A7P0T906

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152048 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000961 AC: 24 AN: 249842 AF XY: 0.0000888

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000320

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000885

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1460064 Hom.: 0 Cov.: 31 AF XY: 0.0000606 AC XY: 44 AN XY: 726276

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.000269 AC: 12 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.0000767 AC: 2 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 85958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000603 AC: 67 AN: 1110998

Other (OTH) AF: 0.0000332 AC: 2 AN: 60312

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152166 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74404

African (AFR) AF: 0.00 AC: 0 AN: 41502

American (AMR) AF: 0.000262 AC: 4 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

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

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000102 Hom.: 0

Bravo AF: 0.0000869

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000596

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.023
DANN	Benign	0.41
PhyloP100		-1.5

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: rs150482005; hg19: chr13-111274582;