rs11107851

Variant names:

• chr12-94995067-T-C
• rs11107851
• NM_018838.5:c.170-810A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

NDUFA12 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 23

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NDUFA12	NM_018838.5	c.170-810A>G		intron_variant	Intron 2 of 3	ENST00000327772.7	NP_061326.1
NDUFA12	NM_001258338.2	c.169+7672A>G		intron_variant	Intron 2 of 2		NP_001245267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA12	ENST00000327772.7	c.170-810A>G		intron_variant	Intron 2 of 3	1	NM_018838.5	ENSP00000330737.2

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

African (AFR) AF: 0.138 AC: 5731 AN: 41484

American (AMR) AF: 0.289 AC: 4421 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 900 AN: 3468

East Asian (EAS) AF: 0.418 AC: 2161 AN: 5170

South Asian (SAS) AF: 0.209 AC: 1006 AN: 4812

European-Finnish (FIN) AF: 0.169 AC: 1791 AN: 10590

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15896 AN: 67976

Other (OTH) AF: 0.219 AC: 462 AN: 2112

Alfa AF: 0.227 Hom.: 6680

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
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11107851; hg19: chr12-95388843;