21-42893343-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_021075.4(NDUFV3):c.10C>T(p.Pro4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,538,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

NDUFV3
NM_021075.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.93

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037558377).

BP6

Variant 21-42893343-C-T is Benign according to our data. Variant chr21-42893343-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3034982.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021075.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFV3	NM_021075.4	MANE Select	c.10C>T	p.Pro4Ser	missense	Exon 1 of 4	NP_066553.3
	NDUFV3	NM_001001503.2		c.10C>T	p.Pro4Ser	missense	Exon 1 of 3	NP_001001503.1	P56181-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFV3	ENST00000354250.7	TSL:1 MANE Select	c.10C>T	p.Pro4Ser	missense	Exon 1 of 4	ENSP00000346196.2	P56181-2
NDUFV3	ENST00000340344.4	TSL:1	c.10C>T	p.Pro4Ser	missense	Exon 1 of 3	ENSP00000342895.3	P56181-1
NDUFV3	ENST00000942160.1		c.10C>T	p.Pro4Ser	missense	Exon 1 of 4	ENSP00000612219.1

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000231

AC:

AN:

134272

AF XY:

0.000178

show subpopulations

Gnomad AFR exome

AF:

0.00316

Gnomad AMR exome

AF:

0.000409

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000106

AC:

147

AN:

1386148

Hom.:

Cov.:

AF XY:

0.0000804

AC XY:

AN XY:

684076

show subpopulations

African (AFR)

AF:

0.00362

AC:

114

AN:

31482

American (AMR)

AF:

0.000420

AC:

AN:

35674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25134

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35706

South Asian (SAS)

AF:

0.00

AC:

AN:

79128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4204

European-Non Finnish (NFE)

AF:

0.00000742

AC:

AN:

1078368

Other (OTH)

AF:

0.000139

AC:

AN:

57708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00105

AC:

160

AN:

152358

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00327

AC:

136

AN:

41590

American (AMR)

AF:

0.00111

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000104

Hom.:

Bravo

AF:

0.00124

ExAC

AF:

0.000267

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

NDUFV3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0040

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.0066

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.42

M_CAP

Benign

0.0047

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.1

PhyloP100

-1.9

PrimateAI

Benign

0.45

PROVEAN

Benign

0.61

REVEL

Benign

0.021

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.041

MutPred

0.22

Loss of catalytic residue at P4 (P = 0.0134)

MVP

0.30

MPC

0.086

ClinPred

0.0092

GERP RS

-2.2

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.085

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over