Variant chr11-67607007-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_007103.4(NDUFV1):c.3G>T(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NDUFV1
NM_007103.4 start_lost

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.44

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 Pathogenic. Variant got 12 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 11-67607007-G-T is Pathogenic according to our data. Variant chr11-67607007-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3600152.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFV1	NM_007103.4 link	c.3G>T	p.Met1?	start_lost	1/10	ENST00000322776.11	NP_009034.2	P49821-1E5KNH5
NDUFV1	NM_001166102.2 link	c.3G>T	p.Met1?	start_lost	1/10		NP_001159574.1	P49821-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFV1	ENST00000322776.11 link	c.3G>T	p.Met1?	start_lost	1/10	1	NM_007103.4	ENSP00000322450.6		P49821-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1458690

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725482

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mitochondrial complex 1 deficiency, nuclear type 4

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Uncertain

0.070

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

T;T;.;T;.;T

Eigen

Benign

-0.090

Eigen_PC

Benign

0.030

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.90

.;D;D;D;D;D

M_CAP

Pathogenic

0.91

MetaRNN

Pathogenic

0.98

D;D;D;D;D;D

MetaSVM

Uncertain

-0.22

PROVEAN

Benign

-0.25

.;N;N;N;N;N

REVEL

Uncertain

0.45

Sift

Uncertain

0.017

.;D;T;T;D;T

Sift4G

Uncertain

0.032

.;D;T;T;D;T

Polyphen

0.0030

B;B;B;B;.;.

Vest4

0.86, 0.67, 0.88

MutPred

0.91

Gain of catalytic residue at M1 (P = 0.0245);Gain of catalytic residue at M1 (P = 0.0245);Gain of catalytic residue at M1 (P = 0.0245);Gain of catalytic residue at M1 (P = 0.0245);Gain of catalytic residue at M1 (P = 0.0245);Gain of catalytic residue at M1 (P = 0.0245);

MVP

0.89

ClinPred

1.0

GERP RS

4.3

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.76

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over