rs12618573

Positions:

• chr2-239904221-G-A
• chr2-239904221-G-C
• chr2-239904221-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA10	NR_136158.2	n.4349+8028C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA10	ENST00000419408.5	c.295-8907C>T		intron_variant		5		ENSP00000408055
NDUFA10	ENST00000679183.1	c.*220+8028C>T		intron_variant, NMD_transcript_variant				ENSP00000503016
NDUFA10	ENST00000677057.1	n.4404+8028C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.536

Alfa AF: 0.479 Hom.: 4251

Bravo AF: 0.518

Asia WGS AF: 0.589 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12618573; hg19: chr2-240843638;