rs7133343

chr12-94927174-A-Cchr12-94927174-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_001749264.2(LOC105369915):n.242+843T>G variant causes a intron, non coding transcript 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: LOC105369915 XR_001749264.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

Genes affected

LOC105369915 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LOC105369915	XR_001749264.2	n.242+843T>G		intron_variant, non_coding_transcript_variant
LOC105369915	XR_945226.2	n.242+843T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA12	ENST00000552205.6	c.*18+843T>G		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.711

Alfa AF: 0.684 Hom.: 42715

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7133343; hg19: chr12-95320950;