rs2083411

Positions:

• chr2-240022311-T-A
• chr2-240022311-T-C
• chr2-240022311-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004544.4(NDUFA10):​c.105A>T​(p.Lys35Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K35K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NDUFA10 NM_004544.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.094284296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA10	NM_004544.4	c.105A>T	p.Lys35Asn	missense_variant	2/10	ENST00000252711.7	NP_004535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA10	ENST00000252711.7	c.105A>T	p.Lys35Asn	missense_variant	2/10	1	NM_004544.4	ENSP00000252711	P4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	2.3
DANN	Benign	0.88
DEOGEN2	Benign	0.0019	T;.;.;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.055	N
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.094	T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.4	L;.;.;.;L;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.22	N;N;.;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.43	T;T;.;T;T;T
Sift4G	Benign	0.45	T;T;T;.;T;T
Polyphen		0.0040	B;.;.;.;.;P
Vest4		0.091
MutPred		0.39		Loss of methylation at K35 (P = 0.0013);Loss of methylation at K35 (P = 0.0013);Loss of methylation at K35 (P = 0.0013);Loss of methylation at K35 (P = 0.0013);Loss of methylation at K35 (P = 0.0013);Loss of methylation at K35 (P = 0.0013);
MVP		0.81
MPC		0.18
ClinPred		0.051	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.40

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: rs2083411; hg19: chr2-240961728;