rs11107847

Variant names:

• chr12-94993015-G-A
• rs11107847
• NM_018838.5:c.257+1155C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018838.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA12	NM_018838.5	MANE Select	c.257+1155C>T		intron	N/A	NP_061326.1	Q9UI09-1
	NDUFA12	NM_001258338.2		c.169+9724C>T		intron	N/A	NP_001245267.1	Q9UI09-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA12	ENST00000327772.7	TSL:1 MANE Select	c.257+1155C>T		intron	N/A	ENSP00000330737.2	Q9UI09-1
	NDUFA12	ENST00000917666.1		c.290+1155C>T		intron	N/A	ENSP00000587725.1
	NDUFA12	ENST00000917665.1		c.257+1155C>T		intron	N/A	ENSP00000587724.1

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

African (AFR) AF: 0.208 AC: 8640 AN: 41476

American (AMR) AF: 0.370 AC: 5648 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3472

East Asian (EAS) AF: 0.419 AC: 2165 AN: 5170

South Asian (SAS) AF: 0.324 AC: 1566 AN: 4826

European-Finnish (FIN) AF: 0.277 AC: 2924 AN: 10566

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25125 AN: 67964

Other (OTH) AF: 0.323 AC: 682 AN: 2112

Alfa AF: 0.350 Hom.: 28534

Bravo AF: 0.314

Asia WGS AF: 0.346 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.015
DANN	Benign	0.21
PhyloP100		-2.8
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: rs11107847; hg19: chr12-95386791;