rs1962412

chr17-48892897-T-Cchr17-48892897-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005175.3(ATP5MC1):c.-23T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 156,470 control chromosomes in the GnomAD database, including 33,187 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 0.64 (31906 hom., cov: 29)
  • Exomes 𝑓: 0.71 (1281 hom.)
• Consequence: ATP5MC1 NM_005175.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.918

Genes affected

ATP5MC1 (HGNC:841): (ATP synthase membrane subunit c locus 1) 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 a single representative of the other 3. The proton channel seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene is one of three genes that encode subunit c of the proton channel. Each of the three genes have distinct mitochondrial import sequences but encode the identical mature protein. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP5MC1	NM_005175.3	c.-23T>C		5_prime_UTR_variant	1/5	ENST00000393366.7
LOC105371814	NR_135674.1	n.46-220A>G		intron_variant, non_coding_transcript_variant
ATP5MC1	NM_001002027.2	c.-10+57T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP5MC1	ENST00000393366.7	c.-23T>C		5_prime_UTR_variant	1/5	1	NM_005175.3	P1
	ENST00000508743.1	n.46-220A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97224 AN: 151384 Hom.: 31900 Cov.: 29

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.713 AC: 3540 AN: 4968 Hom.: 1281 Cov.: 0 AF XY: 0.711 AC XY: 2281 AN XY: 3206

Gnomad4 AFR exome AF: 0.542

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.519

Gnomad4 EAS exome AF: 0.827

Gnomad4 SAS exome AF: 0.713

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.729

Gnomad4 OTH exome AF: 0.726

GnomAD4 genome AF: 0.642 AC: 97261 AN: 151502 Hom.: 31906 Cov.: 29 AF XY: 0.642 AC XY: 47518 AN XY: 73982

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.652

Alfa AF: 0.677 Hom.: 25066

Bravo AF: 0.623

Asia WGS AF: 0.755 AC: 2622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	18
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1962412; hg19: chr17-46970259; COSMIC: COSV63506238; COSMIC: COSV63506238;