rs11107847

chr12-94993015-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+1155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,050 control chromosomes in the GnomAD database, including 8,064 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 0.32 (8064 hom., cov: 32)
• Consequence: NDUFA12 NM_018838.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.78

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA12	NM_018838.5	c.257+1155C>T		intron_variant		ENST00000327772.7
NDUFA12	NM_001258338.2	c.169+9724C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA12	ENST00000327772.7	c.257+1155C>T		intron_variant		1	NM_018838.5	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48255 AN: 151932 Hom.: 8061 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.317 AC: 48270 AN: 152050 Hom.: 8064 Cov.: 32 AF XY: 0.315 AC XY: 23392 AN XY: 74328

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.323

Alfa AF: 0.361 Hom.: 18790

Bravo AF: 0.314

Asia WGS AF: 0.346 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.015
Dann	Benign	0.21

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: rs11107847; hg19: chr12-95386791;