rs7133343

Variant names:

• chr12-94927174-A-C
• rs7133343
• ENST00000552205.6:n.*18+843T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-94927174-A-C
• chr12-94927174-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000552205.6(NDUFA12):​n.*18+843T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 150,530 control chromosomes in the GnomAD database, including 38,122 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 0.71 (38122 hom., cov: 27)
• Consequence: NDUFA12 ENST00000552205.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 2 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

LOC105369915 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369915	XR_001749264.2	n.242+843T>G		intron_variant	Intron 1 of 2
LOC105369915	XR_945226.2	n.242+843T>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA12	ENST00000552205.6	n.*18+843T>G		intron_variant	Intron 4 of 5	5		ENSP00000449144.2

Frequencies

GnomAD3 genomes AF: 0.710 AC: 106767 AN: 150438 Hom.: 38086 Cov.: 27

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.710 AC: 106842 AN: 150530 Hom.: 38122 Cov.: 27 AF XY: 0.710 AC XY: 52104 AN XY: 73418

African (AFR) AF: 0.781 AC: 32121 AN: 41106

American (AMR) AF: 0.748 AC: 11279 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2401 AN: 3458

East Asian (EAS) AF: 0.726 AC: 3737 AN: 5146

South Asian (SAS) AF: 0.655 AC: 3116 AN: 4756

European-Finnish (FIN) AF: 0.604 AC: 5989 AN: 9920

Middle Eastern (MID) AF: 0.710 AC: 206 AN: 290

European-Non Finnish (NFE) AF: 0.678 AC: 45940 AN: 67786

Other (OTH) AF: 0.711 AC: 1485 AN: 2088

Alfa AF: 0.689 Hom.: 54814

Bravo AF: 0.724

Asia WGS AF: 0.716 AC: 2491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.69
PhyloP100		-0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7133343; hg19: chr12-95320950;