rs11170631

Variant names:

• chr12-53647408-T-C
• rs11170631
• ENST00000550241.1:n.66-14342A>G

Variant summary

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

The ENST00000550241.1(ATP5MC2):​n.66-14342A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,978 control chromosomes in the GnomAD database, including 14,351 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 0.40 (14351 hom., cov: 31)
• Consequence: ATP5MC2 ENST00000550241.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 26 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5MC2	ENST00000550241.1	n.66-14342A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61026 AN: 151860 Hom.: 14325 Cov.: 31

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.402 AC: 61098 AN: 151978 Hom.: 14351 Cov.: 31 AF XY: 0.396 AC XY: 29413 AN XY: 74298

African (AFR) AF: 0.655 AC: 27134 AN: 41426

American (AMR) AF: 0.393 AC: 5995 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3466

East Asian (EAS) AF: 0.368 AC: 1902 AN: 5168

South Asian (SAS) AF: 0.245 AC: 1182 AN: 4820

European-Finnish (FIN) AF: 0.253 AC: 2675 AN: 10578

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19832 AN: 67952

Other (OTH) AF: 0.372 AC: 785 AN: 2112

Alfa AF: 0.333 Hom.: 20421

Bravo AF: 0.428

Asia WGS AF: 0.318 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs11170631; hg19: chr12-54041192;