chr12-53678223-A-G

Position:

• chr12-53678223-A-G

Variant summary

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

The XM_047428989.1(ATP5MC2):​c.-32+3178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,068 control chromosomes in the GnomAD database, including 7,507 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 0.31 (7507 hom., cov: 32)
• Consequence: ATP5MC2 XM_047428989.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

Genes affected

ATP5MC2 (HGNC:842): (ATP synthase membrane subunit c locus 2) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and single representatives of the gamma, delta, and epsilon subunits. The proton channel likely has nine subunits (a, b, c, d, e, f, g, F6 and 8). There are three separate genes which encode subunit c of the proton channel and they specify precursors with different import sequences but identical mature proteins. The protein encoded by this gene is one of three precursors of subunit c. This gene has multiple pseudogenes. [provided by RefSeq, Jan 2018]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP5MC2	XM_047428989.1	c.-32+3178T>C		intron_variant			XP_047284945.1
		n.53678223A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47117 AN: 151950 Hom.: 7501 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.310 AC: 47140 AN: 152068 Hom.: 7507 Cov.: 32 AF XY: 0.307 AC XY: 22854 AN XY: 74344

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.313

Alfa AF: 0.301 Hom.: 1009

Bravo AF: 0.323

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.6
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12818213; hg19: chr12-54072007;