2-240005219-A-G

Position:

• chr2-240005219-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_004544.4(NDUFA10):​c.881T>C​(p.Leu294Pro) variant causes a missense 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDUFA10 NM_004544.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.02

Genes affected

NDUFA10 (HGNC:7684): (NADH:ubiquinone oxidoreductase subunit A10) The protein encoded by this gene is a component of 42 kDa complex I, the first enzyme complex in the electron transport chain of mitochondria. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. A mutation in this gene was found in an individual with Leigh syndrome. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.895
• PP5: Variant 2-240005219-A-G is Pathogenic according to our data. Variant chr2-240005219-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 372194.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA10	NM_004544.4	c.881T>C	p.Leu294Pro	missense_variant	8/10	ENST00000252711.7	NP_004535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA10	ENST00000252711.7	c.881T>C	p.Leu294Pro	missense_variant	8/10	1	NM_004544.4	ENSP00000252711	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Mitochondrial complex 1 deficiency, nuclear type 22 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T;.;.;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.89	D;D;D;D;D;D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Uncertain	2.1	.;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.9	D;D;D;.;D;D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0050	D;D;D;.;D;D
Sift4G	Uncertain	0.0020	D;T;T;T;D;D
Polyphen		1.0	.;D;.;.;.;.
Vest4		0.95, 0.93, 0.95, 0.90
MutPred		0.72		.;.;.;.;.;Loss of stability (P = 0.0059);
MVP		0.98
MPC		0.75
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.87
gMVP		0.87

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: rs1057519414; hg19: chr2-240944636;