rs11107845

Variant names:

• chr12-94990427-G-A
• rs11107845
• NM_018838.5:c.257+3743C>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+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
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA12	NM_018838.5	MANE Select	c.257+3743C>T		intron	N/A	NP_061326.1
	NDUFA12	NM_001258338.2		c.169+12312C>T		intron	N/A	NP_001245267.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA12	ENST00000327772.7	TSL:1 MANE Select	c.257+3743C>T		intron	N/A	ENSP00000330737.2
	NDUFA12	ENST00000684171.1		c.257+3743C>T		intron	N/A	ENSP00000506808.1
	NDUFA12	ENST00000547986.5	TSL:2	c.169+12312C>T		intron	N/A	ENSP00000450130.1

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

African (AFR) AF: 0.0620 AC: 2572 AN: 41484

American (AMR) AF: 0.136 AC: 2074 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0779 AC: 270 AN: 3468

East Asian (EAS) AF: 0.156 AC: 805 AN: 5164

South Asian (SAS) AF: 0.0898 AC: 432 AN: 4810

European-Finnish (FIN) AF: 0.0298 AC: 315 AN: 10584

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0767 AC: 5212 AN: 67974

Other (OTH) AF: 0.0986 AC: 208 AN: 2110

Alfa AF: 0.0802 Hom.: 383

Bravo AF: 0.0895

Asia WGS AF: 0.149 AC: 516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.52
DANN	Benign	0.75
PhyloP100		-0.38
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: rs11107845; hg19: chr12-95384203;