NM_182977.3:c.46C>G

Variant names:

• chr5-43609241-C-G
• rs10057103
• NM_182977.3:c.46C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182977.3(NNT):​c.46C>G​(p.Leu16Val) 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. 15/21 in silico tools predict 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. L16L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NNT NM_182977.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

Genes affected

NNT (HGNC:7863): (nicotinamide nucleotide transhydrogenase) This gene encodes an integral protein of the inner mitochondrial membrane. The enzyme couples hydride transfer between NAD(H) and NADP(+) to proton translocation across the inner mitochondrial membrane. Under most physiological conditions, the enzyme uses energy from the mitochondrial proton gradient to produce high concentrations of NADPH. The resulting NADPH is used for biosynthesis and in free radical detoxification. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055696905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NNT	NM_182977.3	c.46C>G	p.Leu16Val	missense_variant	Exon 2 of 22	ENST00000344920.9	NP_892022.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NNT	ENST00000344920.9	c.46C>G	p.Leu16Val	missense_variant	Exon 2 of 22	1	NM_182977.3	ENSP00000343873.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0074	.;T;T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.60	T;T;.;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.056	T;T;T;T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	0.14	.;.;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.010	N;N;N;N
REVEL	Benign	0.29
Sift	Benign	0.51	T;T;T;T
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.0	.;.;B;B
Vest4		0.11
MutPred		0.20		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.44
MPC		0.26
ClinPred		0.052	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.034
gMVP		0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs10057103; hg19: chr5-43609343;