Variant chr21-42903351-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_021075.4(NDUFV3):c.339G>A(p.Pro113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 1,614,102 control chromosomes in the GnomAD database, including 5,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.065 ( 418 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4595 hom. )

Consequence

NDUFV3
NM_021075.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.597

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 21-42903351-G-A is Benign according to our data. Variant chr21-42903351-G-A is described in ClinVar as [Benign]. Clinvar id is 3056561.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.597 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NDUFV3	NM_021075.4 linkuse as main transcript	c.339G>A	p.Pro113=	synonymous_variant	3/4	ENST00000354250.7	NP_066553.3
NDUFV3	XM_011529586.3 linkuse as main transcript	c.339G>A	p.Pro113=	synonymous_variant	3/5		XP_011527888.1
NDUFV3	NM_001001503.2 linkuse as main transcript	c.170-5513G>A		intron_variant			NP_001001503.1
NDUFV3	XM_017028359.2 linkuse as main transcript	c.170-3489G>A		intron_variant			XP_016883848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFV3	ENST00000354250.7 linkuse as main transcript	c.339G>A	p.Pro113=	synonymous_variant	3/4	1	NM_021075.4	ENSP00000346196		P56181-2
NDUFV3	ENST00000340344.4 linkuse as main transcript	c.170-5513G>A		intron_variant		1		ENSP00000342895	P1	P56181-1
NDUFV3	ENST00000460259.1 linkuse as main transcript	n.862G>A		non_coding_transcript_exon_variant	5/6	2
NDUFV3	ENST00000460740.1 linkuse as main transcript	n.231G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0653

AC:

9928

AN:

152100

Hom.:

417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0488

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0779

Gnomad ASJ

AF:

0.0686

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.0349

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0647

Gnomad OTH

AF:

0.0608

GnomAD3 exomes

AF:

0.0820

AC:

20610

AN:

251490

Hom.:

1002

AF XY:

0.0853

AC XY:

11599

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0485

Gnomad AMR exome

AF:

0.0888

Gnomad ASJ exome

AF:

0.0665

Gnomad EAS exome

AF:

0.142

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.0320

Gnomad NFE exome

AF:

0.0694

Gnomad OTH exome

AF:

0.0777

GnomAD4 exome

AF:

0.0737

AC:

107699

AN:

1461884

Hom.:

4595

Cov.:

AF XY:

0.0763

AC XY:

55522

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0467

Gnomad4 AMR exome

AF:

0.0880

Gnomad4 ASJ exome

AF:

0.0671

Gnomad4 EAS exome

AF:

0.155

Gnomad4 SAS exome

AF:

0.145

Gnomad4 FIN exome

AF:

0.0352

Gnomad4 NFE exome

AF:

0.0675

Gnomad4 OTH exome

AF:

0.0733

GnomAD4 genome

AF:

0.0653

AC:

9943

AN:

152218

Hom.:

418

Cov.:

AF XY:

0.0669

AC XY:

4978

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0491

Gnomad4 AMR

AF:

0.0778

Gnomad4 ASJ

AF:

0.0686

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.0349

Gnomad4 NFE

AF:

0.0647

Gnomad4 OTH

AF:

0.0602

Alfa

AF:

0.0693

Hom.:

618

Bravo

AF:

0.0682

Asia WGS

AF:

0.132

AC:

460

AN:

3478

EpiCase

AF:

0.0658

EpiControl

AF:

0.0674

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NDUFV3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.0

DANN

Benign

0.41

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over