3-16270968-G-A

Variant names:

• chr3-16270968-G-A
• NM_138381.5:c.16G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138381.5(OXNAD1):​c.16G>A​(p.Val6Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OXNAD1 NM_138381.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.345
• Publications: 0 publications found

Genes affected

OXNAD1 (HGNC:25128): (oxidoreductase NAD binding domain containing 1) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03772849).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXNAD1	NM_138381.5	c.16G>A	p.Val6Ile	missense_variant	Exon 3 of 9	ENST00000285083.10	NP_612390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXNAD1	ENST00000285083.10	c.16G>A	p.Val6Ile	missense_variant	Exon 3 of 9	1	NM_138381.5	ENSP00000285083.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16G>A (p.V6I) alteration is located in exon 3 (coding exon 1) of the OXNAD1 gene. This alteration results from a G to A substitution at nucleotide position 16, causing the valine (V) at amino acid position 6 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.8
DANN	Benign	0.94
DEOGEN2	Benign	0.014	T;T;T;T;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.63	T;.;T;.;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.038	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	.;L;L;.;.
PhyloP100		0.34
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.020	.;N;.;.;.
REVEL	Benign	0.024
Sift	Benign	0.38	.;T;.;.;.
Sift4G	Benign	0.28	T;T;T;T;T
Polyphen		0.043	.;B;B;.;.
Vest4		0.054
MutPred		0.35		.;Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);.;Loss of sheet (P = 0.0104);
MVP		0.055
MPC		0.031
ClinPred		0.076	T
GERP RS		1.9
Varity_R		0.022
gMVP		0.22
Mutation Taster		=97/3	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

hg19: chr3-16312475;