Variant rs8875 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004549.6(NDUFC2):c.136C>G(p.Leu46Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,561,654 control chromosomes in the GnomAD database, including 38,804 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.18 ( 2950 hom., cov: 31)

Exomes 𝑓: 0.22 ( 35854 hom. )

Consequence

NDUFC2
NM_004549.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0690

Variant links:

Genes affected

NDUFC2 (HGNC:7706): (NADH:ubiquinone oxidoreductase subunit C2) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Part of mitochondrial respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency. [provided by Alliance of Genome Resources, Apr 2022]

NDUFC2 links:

NDUFC2-KCTD14 (HGNC:):

NDUFC2-KCTD14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005250782).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFC2	NM_004549.6 linkuse as main transcript	c.136C>G	p.Leu46Val	missense_variant	1/3	ENST00000281031.5
NDUFC2-KCTD14	NM_001203262.2 linkuse as main transcript	c.136C>G	p.Leu46Val	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFC2	ENST00000281031.5 linkuse as main transcript	c.136C>G	p.Leu46Val	missense_variant	1/3	1	NM_004549.6	P1	O95298-1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27178

AN:

152054

Hom.:

2947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0623

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.0729

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.203

GnomAD3 exomes

AF:

0.202

AC:

33765

AN:

167340

Hom.:

3709

AF XY:

0.205

AC XY:

18311

AN XY:

89310

show subpopulations

Gnomad AFR exome

AF:

0.0584

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.0816

Gnomad SAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.221

AC:

312071

AN:

1409482

Hom.:

35854

Cov.:

AF XY:

0.222

AC XY:

154302

AN XY:

696332

show subpopulations

Gnomad4 AFR exome

AF:

0.0584

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.305

Gnomad4 EAS exome

AF:

0.0677

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.179

AC:

27190

AN:

152172

Hom.:

2950

Cov.:

AF XY:

0.178

AC XY:

13213

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0621

Gnomad4 AMR

AF:

0.235

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.0736

Gnomad4 SAS

AF:

0.198

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.235

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.232

Hom.:

1416

Bravo

AF:

0.176

TwinsUK

AF:

0.231

AC:

858

ALSPAC

AF:

0.246

AC:

950

ESP6500AA

AF:

0.0708

AC:

308

ESP6500EA

AF:

0.219

AC:

1859

ExAC

AF:

0.170

AC:

19507

Asia WGS

AF:

0.135

AC:

468

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.013

T;T;.;.;T;.;T;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.20

T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0053

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

.;L;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.21

N;N;.;.;N;N;N;N;N

REVEL

Benign

0.020

Sift

Benign

0.20

T;T;.;.;T;T;T;T;T

Sift4G

Benign

0.52

T;T;T;T;T;T;T;T;T

Polyphen

0.0030

.;.;.;.;B;.;.;.;.

Vest4

0.11

MPC

0.58, 0.56

ClinPred

0.0090

GERP RS

-0.89

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.14

gMVP

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over