rs148352905

Variant names:

• chr11-67607047-C-G
• rs148352905
• NM_007103.4:c.43C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-67607047-C-G
• chr11-67607047-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007103.4(NDUFV1):​c.43C>G​(p.Arg15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R15W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDUFV1 NM_007103.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFV1	NM_007103.4	c.43C>G	p.Arg15Gly	missense_variant	Exon 1 of 10	ENST00000322776.11	NP_009034.2
NDUFV1	NM_001166102.2	c.43C>G	p.Arg15Gly	missense_variant, splice_region_variant	Exon 1 of 10		NP_001159574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFV1	ENST00000322776.11	c.43C>G	p.Arg15Gly	missense_variant	Exon 1 of 10	1	NM_007103.4	ENSP00000322450.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Benign	0.83
DEOGEN2	Benign	0.22	T;T;.;T;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.75	.;T;T;T;T;T
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.81	L;L;L;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	.;N;N;N;N;N
REVEL	Uncertain	0.38
Sift	Benign	0.078	.;T;T;T;T;T
Sift4G	Benign	0.24	.;T;T;T;T;T
Polyphen		0.0	B;B;B;B;.;.
Vest4		0.58, 0.62, 0.49
MutPred		0.46		Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);
MVP		0.89
MPC		0.33
ClinPred		0.54	D
GERP RS		3.7
Varity_R		0.20
gMVP		0.82

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

Other links and lift over

dbSNP: rs148352905; hg19: chr11-67374518;