Variant 11-67607018-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007103.4(NDUFV1):c.14G>A(p.Arg5Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NDUFV1
NM_007103.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.79

Variant links:

Genes affected

NDUFV1 (HGNC:7716): (NADH:ubiquinone oxidoreductase core subunit V1) The mitochondrial respiratory chain provides energy to cells via oxidative phosphorylation and consists of four membrane-bound electron-transporting protein complexes (I-IV) and an ATP synthase (complex V). This gene encodes a 51 kDa subunit of the NADH:ubiquinone oxidoreductase complex I; a large complex with at least 45 nuclear and mitochondrial encoded subunits that liberates electrons from NADH and channels them to ubiquinone. This subunit carries the NADH-binding site as well as flavin mononucleotide (FMN)- and Fe-S-biding sites. Defects in complex I are a common cause of mitochondrial dysfunction; a syndrome that occurs in approximately 1 in 10,000 live births. Mitochondrial complex I deficiency is linked to myopathies, encephalomyopathies, and neurodegenerative disorders such as Parkinson's disease and Leigh syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2009]

NDUFV1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24994794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFV1	NM_007103.4 linkuse as main transcript	c.14G>A	p.Arg5Gln	missense_variant	1/10	ENST00000322776.11	NP_009034.2
NDUFV1	NM_001166102.2 linkuse as main transcript	c.14G>A	p.Arg5Gln	missense_variant	1/10		NP_001159574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFV1	ENST00000322776.11 linkuse as main transcript	c.14G>A	p.Arg5Gln	missense_variant	1/10	1	NM_007103.4	ENSP00000322450	P1	P49821-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458258

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725324

show subpopulations

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2021

The c.14G>A (p.R5Q) alteration is located in exon 1 (coding exon 1) of the NDUFV1 gene. This alteration results from a G to A substitution at nucleotide position 14, causing the arginine (R) at amino acid position 5 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;.;T;.;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.86

.;D;D;D;D;D

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.25

T;T;T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.4

L;L;L;.;.;.

MutationTaster

Benign

0.79

D;D;N;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.23

.;N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.13

.;T;T;T;T;T

Sift4G

Benign

0.20

.;T;T;T;T;T

Polyphen

0.67

P;P;B;B;.;.

Vest4

0.39, 0.46, 0.45

MutPred

0.57

Loss of MoRF binding (P = 0.0353);Loss of MoRF binding (P = 0.0353);Loss of MoRF binding (P = 0.0353);Loss of MoRF binding (P = 0.0353);Loss of MoRF binding (P = 0.0353);Loss of MoRF binding (P = 0.0353);

MVP

0.88

MPC

0.30

ClinPred

0.43

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.076

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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