13-110615686-C-A

Variant names:

• chr13-110615686-C-A
• rs781696886
• NM_001242882.2:c.46+39C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018210.4(NAXD):​c.12C>A​(p.Arg4Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,372,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R4R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: NAXD NM_018210.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• 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-AS1 (HGNC:56341): (NAXD antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.499 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018210.4. 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.46+39C>A		intron	N/A	NP_001229811.1	A0A7P0T9D8
	NAXD	NM_018210.4		c.12C>A	p.Arg4Arg	synonymous	Exon 1 of 10	NP_060680.2	Q8IW45-2
	NAXD	NM_001242881.2		c.12C>A	p.Arg4Arg	synonymous	Exon 1 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.46+39C>A		intron	N/A	ENSP00000505619.1	A0A7P0T9D8
	NAXD	ENST00000309957.3	TSL:2	c.12C>A	p.Arg4Arg	synonymous	Exon 1 of 10	ENSP00000311984.2	Q8IW45-2
	NAXD	ENST00000680505.1		c.12C>A	p.Arg4Arg	synonymous	Exon 1 of 10	ENSP00000504986.1	Q8IW45-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1372048 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 680006

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28782

American (AMR) AF: 0.00 AC: 0 AN: 34690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24140

East Asian (EAS) AF: 0.00 AC: 0 AN: 31316

South Asian (SAS) AF: 0.00 AC: 0 AN: 78322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1074310

Other (OTH) AF: 0.00 AC: 0 AN: 56850

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.9
DANN	Benign	0.57
PhyloP100		-0.50
PromoterAI		0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs781696886; hg19: chr13-111268033;