2-239904221-G-A

Variant names:

• chr2-239904221-G-A
• rs12618573
• ENST00000419408.5:c.295-8907C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000419408.5(NDUFA10):​c.295-8907C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,930 control chromosomes in the GnomAD database, including 19,877 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (19877 hom., cov: 31)
• Consequence: NDUFA10 ENST00000419408.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 3 publications found

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]

NDUFA10 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 22

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000419408.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA10	NR_136158.2		n.4349+8028C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA10	ENST00000419408.5	TSL:5	c.295-8907C>T		intron	N/A	ENSP00000408055.1
	NDUFA10	ENST00000677057.1		n.4404+8028C>T		intron	N/A
	NDUFA10	ENST00000679183.1		n.*220+8028C>T		intron	N/A	ENSP00000503016.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76873 AN: 151812 Hom.: 19860 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.506 AC: 76929 AN: 151930 Hom.: 19877 Cov.: 31 AF XY: 0.512 AC XY: 37992 AN XY: 74266

African (AFR) AF: 0.461 AC: 19110 AN: 41418

American (AMR) AF: 0.655 AC: 10016 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1825 AN: 3464

East Asian (EAS) AF: 0.638 AC: 3292 AN: 5158

South Asian (SAS) AF: 0.609 AC: 2932 AN: 4818

European-Finnish (FIN) AF: 0.438 AC: 4625 AN: 10548

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 33349 AN: 67928

Other (OTH) AF: 0.536 AC: 1131 AN: 2112

Alfa AF: 0.498 Hom.: 18744

Bravo AF: 0.518

Asia WGS AF: 0.589 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.46
PhyloP100		0.095

Splicing

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

Other links and lift over

dbSNP: rs12618573; hg19: chr2-240843638;