17-48892897-T-G

Variant names:

• chr17-48892897-T-G
• rs1962412
• NM_005175.3:c.-23T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005175.3(ATP5MC1):​c.-23T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATP5MC1 NM_005175.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.918
• Publications: 34 publications found

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]

ENSG00000293025 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005175.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5MC1	NM_005175.3	MANE Select	c.-23T>G		5_prime_UTR	Exon 1 of 5	NP_005166.1	P05496
	ATP5MC1	NM_001002027.2		c.-10+57T>G		intron	N/A	NP_001002027.1	P05496
	LOC105371814	NR_135674.1		n.46-220A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5MC1	ENST00000393366.7	TSL:1 MANE Select	c.-23T>G		5_prime_UTR	Exon 1 of 5	ENSP00000377033.2	P05496
	ATP5MC1	ENST00000355938.9	TSL:1	c.-10+57T>G		intron	N/A	ENSP00000348205.5	P05496
	ATP5MC1	ENST00000938824.1		c.-23T>G		5_prime_UTR	Exon 1 of 6	ENSP00000608883.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 5004 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3230

African (AFR) AF: 0.00 AC: 0 AN: 48

American (AMR) AF: 0.00 AC: 0 AN: 304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 54

East Asian (EAS) AF: 0.00 AC: 0 AN: 114

South Asian (SAS) AF: 0.00 AC: 0 AN: 1110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2908

Other (OTH) AF: 0.00 AC: 0 AN: 194

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 35922

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.88
PhyloP100		0.92
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1962412; hg19: chr17-46970259;