chr2-239904933-G-A

Variant names:

• chr2-239904933-G-A
• rs13402622
• ENST00000419408.5:c.295-9619C>T

Variant summary

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

The NR_136158.2(NDUFA10):​n.4349+7316C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,030 control chromosomes in the GnomAD database, including 37,388 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 0.70 (37388 hom., cov: 32)
• Consequence: NDUFA10 NR_136158.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 7 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: G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_136158.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA10	NR_136158.2		n.4349+7316C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA10	ENST00000419408.5	TSL:5	c.295-9619C>T		intron	N/A	ENSP00000408055.1	H7C2W5
	NDUFA10	ENST00000677057.1		n.4404+7316C>T		intron	N/A
	NDUFA10	ENST00000679183.1		n.*220+7316C>T		intron	N/A	ENSP00000503016.1	A0A7I2V2N6

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106045 AN: 151910 Hom.: 37360 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.698 AC: 106117 AN: 152030 Hom.: 37388 Cov.: 32 AF XY: 0.702 AC XY: 52162 AN XY: 74330

African (AFR) AF: 0.630 AC: 26102 AN: 41456

American (AMR) AF: 0.793 AC: 12126 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2660 AN: 3472

East Asian (EAS) AF: 0.933 AC: 4802 AN: 5146

South Asian (SAS) AF: 0.682 AC: 3284 AN: 4818

European-Finnish (FIN) AF: 0.728 AC: 7700 AN: 10582

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47025 AN: 67952

Other (OTH) AF: 0.730 AC: 1542 AN: 2112

Alfa AF: 0.698 Hom.: 168324

Bravo AF: 0.704

Asia WGS AF: 0.798 AC: 2775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.87
DANN	Benign	0.35
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs13402622; hg19: chr2-240844350;