rs11107851

Positions:

• chr12-94995067-T-C

Variant summary

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

The NM_018838.5(NDUFA12):​c.170-810A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,092 control chromosomes in the GnomAD database, including 3,778 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 0.21 (3778 hom., cov: 32)
• Consequence: NDUFA12 NM_018838.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA12	NM_018838.5	c.170-810A>G		intron_variant		ENST00000327772.7	NP_061326.1
NDUFA12	NM_001258338.2	c.169+7672A>G		intron_variant			NP_001245267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA12	ENST00000327772.7	c.170-810A>G		intron_variant		1	NM_018838.5	ENSP00000330737	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32483 AN: 151974 Hom.: 3777 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.214 AC: 32490 AN: 152092 Hom.: 3778 Cov.: 32 AF XY: 0.212 AC XY: 15800 AN XY: 74372

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.219

Alfa AF: 0.230 Hom.: 5497

Bravo AF: 0.214

Asia WGS AF: 0.291 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.77

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: rs11107851; hg19: chr12-95388843;