rs886039790

Variant names:

• chr5-43612967-C-G
• NM_182977.3:c.211C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-43612967-C-G
• chr5-43612967-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_182977.3(NNT):​c.211C>G​(p.Arg71Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NNT NM_182977.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NNT	NM_182977.3	c.211C>G	p.Arg71Gly	missense_variant	Exon 3 of 22	ENST00000344920.9	NP_892022.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NNT	ENST00000344920.9	c.211C>G	p.Arg71Gly	missense_variant	Exon 3 of 22	1	NM_182977.3	ENSP00000343873.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	.;D;D;D
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	1.0	D;D;.;D
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.98	D;D;D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Pathogenic	4.5	.;.;H;H
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.9	D;D;D;D
REVEL	Pathogenic	0.87
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	.;.;D;D
Vest4		0.95
MutPred		0.92		Gain of catalytic residue at V72 (P = 0.0478);Gain of catalytic residue at V72 (P = 0.0478);Gain of catalytic residue at V72 (P = 0.0478);Gain of catalytic residue at V72 (P = 0.0478);
MVP		0.94
MPC		1.0
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.96
gMVP		0.98

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-43613069;