rs7965624

Positions:

• chr12-94907877-A-G

Variant summary

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

The XR_001749264.2(LOC105369915):​n.404-10567T>C 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 0.579 in 152,012 control chromosomes in the GnomAD database, including 25,931 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 0.58 (25931 hom., cov: 32)
• Consequence: LOC105369915 XR_001749264.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105369915	XR_001749264.2	n.404-10567T>C		intron_variant, non_coding_transcript_variant
LOC105369915	XR_945226.2	n.514+2356T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA12	ENST00000552205.6	c.*180-10567T>C		intron_variant, NMD_transcript_variant		5
NDUFA12	ENST00000547447.1	n.272+2356T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87938 AN: 151894 Hom.: 25899 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.579 AC: 88022 AN: 152012 Hom.: 25931 Cov.: 32 AF XY: 0.577 AC XY: 42827 AN XY: 74276

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.586

Alfa AF: 0.616 Hom.: 64478

Bravo AF: 0.576

Asia WGS AF: 0.488 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7965624; hg19: chr12-95301653;