chr2-239904933-G-A

Position:

• chr2-239904933-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000419408.5(NDUFA10):​c.295-9619C>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 ENST00000419408.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA10	NR_136158.2	n.4349+7316C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA10	ENST00000419408.5	c.295-9619C>T		intron_variant		5		ENSP00000408055
NDUFA10	ENST00000679183.1	c.*220+7316C>T		intron_variant, NMD_transcript_variant				ENSP00000503016
NDUFA10	ENST00000677057.1	n.4404+7316C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.933

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.730

Alfa AF: 0.700 Hom.: 79189

Bravo AF: 0.704

Asia WGS AF: 0.798 AC: 2775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13402622; hg19: chr2-240844350;