3-16271057-C-G

Variant names:

• chr3-16271057-C-G
• NM_138381.5:c.105C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138381.5(OXNAD1):​c.105C>G​(p.His35Gln) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OXNAD1 NM_138381.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.769
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14681995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXNAD1	NM_138381.5	c.105C>G	p.His35Gln	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.105C>G	p.His35Gln	missense_variant	Exon 3 of 9	1	NM_138381.5	ENSP00000285083.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.105C>G (p.H35Q) alteration is located in exon 3 (coding exon 1) of the OXNAD1 gene. This alteration results from a C to G substitution at nucleotide position 105, causing the histidine (H) at amino acid position 35 to be replaced by a glutamine (Q). 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	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.018	T;T;T;T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.57	T;.;T;.;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	.;M;M;.;.
PhyloP100		0.77
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.91	.;N;.;.;.
REVEL	Benign	0.029
Sift	Uncertain	0.021	.;D;.;.;.
Sift4G	Uncertain	0.016	D;D;D;D;D
Polyphen		0.037	.;B;B;.;.
Vest4		0.42
MutPred		0.41		.;Gain of solvent accessibility (P = 0.0137);Gain of solvent accessibility (P = 0.0137);.;Gain of solvent accessibility (P = 0.0137);
MVP		0.076
MPC		0.066
ClinPred		0.14	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
gMVP		0.16
Mutation Taster		=91/9	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: chr3-16312564;