Variant rs10595 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021075.4(NDUFV3):c.1243G>A(p.Asp415Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,604,424 control chromosomes in the GnomAD database, including 290,981 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 28444 hom., cov: 32)

Exomes 𝑓: 0.60 ( 262537 hom. )

Consequence

NDUFV3
NM_021075.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.773

Variant links:

Genes affected

NDUFV3 (HGNC:7719): (NADH:ubiquinone oxidoreductase subunit V3) The protein encoded by this gene is one of at least forty-one subunits that make up the NADH-ubiquinone oxidoreductase complex. This complex is part of the mitochondrial respiratory chain and serves to catalyze the rotenone-sensitive oxidation of NADH and the reduction of ubiquinone. The encoded protein is one of three proteins found in the flavoprotein fraction of the complex. The specific function of the encoded protein is unknown. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

NDUFV3 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=2.4735414E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NDUFV3	NM_021075.4 linkuse as main transcript	c.1243G>A	p.Asp415Asn	missense_variant	3/4	ENST00000354250.7
NDUFV3	XM_011529586.3 linkuse as main transcript	c.1243G>A	p.Asp415Asn	missense_variant	3/5
NDUFV3	NM_001001503.2 linkuse as main transcript	c.170-4609G>A		intron_variant
NDUFV3	XM_017028359.2 linkuse as main transcript	c.170-2585G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFV3	ENST00000354250.7 linkuse as main transcript	c.1243G>A	p.Asp415Asn	missense_variant	3/4	1	NM_021075.4		P56181-2
NDUFV3	ENST00000340344.4 linkuse as main transcript	c.170-4609G>A		intron_variant		1		P1	P56181-1
NDUFV3	ENST00000460259.1 linkuse as main transcript	n.1766G>A		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91662

AN:

151928

Hom.:

28411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.711

Gnomad AMI

AF:

0.603

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.554

GnomAD3 exomes

AF:

0.549

AC:

126731

AN:

230690

Hom.:

36305

AF XY:

0.556

AC XY:

69411

AN XY:

124932

show subpopulations

Gnomad AFR exome

AF:

0.718

Gnomad AMR exome

AF:

0.338

Gnomad ASJ exome

AF:

0.577

Gnomad EAS exome

AF:

0.330

Gnomad SAS exome

AF:

0.566

Gnomad FIN exome

AF:

0.627

Gnomad NFE exome

AF:

0.607

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.597

AC:

867304

AN:

1452378

Hom.:

262537

Cov.:

AF XY:

0.597

AC XY:

430611

AN XY:

721614

show subpopulations

Gnomad4 AFR exome

AF:

0.716

Gnomad4 AMR exome

AF:

0.345

Gnomad4 ASJ exome

AF:

0.569

Gnomad4 EAS exome

AF:

0.365

Gnomad4 SAS exome

AF:

0.570

Gnomad4 FIN exome

AF:

0.627

Gnomad4 NFE exome

AF:

0.614

Gnomad4 OTH exome

AF:

0.573

GnomAD4 genome

AF:

0.603

AC:

91739

AN:

152046

Hom.:

28444

Cov.:

AF XY:

0.600

AC XY:

44604

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.711

Gnomad4 AMR

AF:

0.427

Gnomad4 ASJ

AF:

0.570

Gnomad4 EAS

AF:

0.339

Gnomad4 SAS

AF:

0.555

Gnomad4 FIN

AF:

0.629

Gnomad4 NFE

AF:

0.600

Gnomad4 OTH

AF:

0.553

Alfa

AF:

0.591

Hom.:

68514

Bravo

AF:

0.589

TwinsUK

AF:

0.615

AC:

2282

ALSPAC

AF:

0.626

AC:

2413

ESP6500AA

AF:

0.705

AC:

3106

ESP6500EA

AF:

0.609

AC:

5240

ExAC

AF:

0.550

AC:

66620

Asia WGS

AF:

0.439

AC:

1531

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0000025

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.6

REVEL

Benign

0.083

Sift

Uncertain

0.021

Sift4G

Benign

0.12

Vest4

0.026

MPC

0.12

ClinPred

0.0070

GERP RS

2.9

gMVP

0.074

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