chr12-94909785-C-T

Position:

• chr12-94909785-C-T

Variant summary

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

The ENST00000547447.1(NDUFA12):​n.272+448G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,882 control chromosomes in the GnomAD database, including 17,675 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 0.47 (17675 hom., cov: 31)
• Consequence: NDUFA12 ENST00000547447.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

Genes affected

NDUFA12 (HGNC:):

NDUFA12 (HGNC:23987): (NADH:ubiquinone oxidoreductase subunit A12) This gene encodes a protein which is part of mitochondrial complex 1, part of the oxidative phosphorylation system in mitochondria. Complex 1 transfers electrons to ubiquinone from NADH which establishes a proton gradient for the generation of ATP. Mutations in this gene are associated with Leigh syndrome due to mitochondrial complex 1 deficiency. Pseudogenes of this gene are located on chromosomes 5 and 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105369915	XR_001749264.2	n.404-12475G>A		intron_variant
LOC105369915	XR_945226.2	n.514+448G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA12	ENST00000547447.1	n.272+448G>A		intron_variant		3
NDUFA12	ENST00000552205.6	n.*180-12475G>A		intron_variant		5		ENSP00000449144.2

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72072 AN: 151764 Hom.: 17661 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.475 AC: 72120 AN: 151882 Hom.: 17675 Cov.: 31 AF XY: 0.471 AC XY: 34952 AN XY: 74214

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.487

Alfa AF: 0.495 Hom.: 10074

Bravo AF: 0.468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.039
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2052741; hg19: chr12-95303561;