rs11107845

chr12-94990427-G-A

Variant summary

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

The NM_018838.5(NDUFA12):c.257+3743C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 152,046 control chromosomes in the GnomAD database, including 560 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 0.080 (560 hom., cov: 31)
• Consequence: NDUFA12 NM_018838.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

Genes affected

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA12	NM_018838.5	c.257+3743C>T		intron_variant		ENST00000327772.7
NDUFA12	NM_001258338.2	c.169+12312C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA12	ENST00000327772.7	c.257+3743C>T		intron_variant		1	NM_018838.5	P1

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 12167 AN: 151928 Hom.: 553 Cov.: 31

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.0953

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

GnomAD4 genome AF: 0.0801 AC: 12181 AN: 152046 Hom.: 560 Cov.: 31 AF XY: 0.0792 AC XY: 5886 AN XY: 74332

Gnomad4 AFR AF: 0.0620

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0779

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.0898

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0767

Gnomad4 OTH AF: 0.0986

Alfa AF: 0.0777 Hom.: 250

Bravo AF: 0.0895

Asia WGS AF: 0.149 AC: 516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.52
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11107845; hg19: chr12-95384203;