chr12-94925509-C-A

Variant names:

• chr12-94925509-C-A
• rs2081595
• ENST00000552205.6:n.*19-703G>T

Variant summary

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

The ENST00000552205.6(NDUFA12):​n.*19-703G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,990 control chromosomes in the GnomAD database, including 16,918 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 0.47 (16918 hom., cov: 32)
• Consequence: NDUFA12 ENST00000552205.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369915	XR_001749264.2	n.243-703G>T		intron_variant	Intron 1 of 2
LOC105369915	XR_945226.2	n.243-703G>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA12	ENST00000552205.6	n.*19-703G>T		intron_variant	Intron 4 of 5	5		ENSP00000449144.2

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71269 AN: 151872 Hom.: 16898 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.469 AC: 71329 AN: 151990 Hom.: 16918 Cov.: 32 AF XY: 0.468 AC XY: 34788 AN XY: 74270

African (AFR) AF: 0.448 AC: 18577 AN: 41436

American (AMR) AF: 0.518 AC: 7916 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1796 AN: 3468

East Asian (EAS) AF: 0.300 AC: 1549 AN: 5156

South Asian (SAS) AF: 0.439 AC: 2117 AN: 4820

European-Finnish (FIN) AF: 0.422 AC: 4456 AN: 10556

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33420 AN: 67956

Other (OTH) AF: 0.480 AC: 1014 AN: 2114

Alfa AF: 0.485 Hom.: 13346

Bravo AF: 0.472

Asia WGS AF: 0.443 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.81
PhyloP100		0.061

Splicing

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

Other links and lift over

dbSNP: rs2081595; hg19: chr12-95319285;