Genetic Variant ATP5MC1:p.Ile14Ser (chr17-48894373-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_005175.3(ATP5MC1):c.41T>G(p.Ile14Ser) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I14N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ATP5MC1
NM_005175.3 missense, splice_region

Scores

Splicing: ADA: 0.1752

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.09

Publications

0 publications found

Variant links:

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]

ATP5MC1 links:

ENSG00000293025 (HGNC:):

ENSG00000293025 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP5MC1	NM_005175.3	MANE Select	c.41T>G	p.Ile14Ser	missense splice_region	Exon 3 of 5	NP_005166.1	P05496
ATP5MC1	NM_001002027.2		c.41T>G	p.Ile14Ser	missense splice_region	Exon 3 of 5	NP_001002027.1	P05496
LOC105371814	NR_135674.1		n.46-1696A>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP5MC1	ENST00000393366.7	TSL:1 MANE Select	c.41T>G	p.Ile14Ser	missense splice_region	Exon 3 of 5	ENSP00000377033.2	P05496
ATP5MC1	ENST00000355938.9	TSL:1	c.41T>G	p.Ile14Ser	missense splice_region	Exon 3 of 5	ENSP00000348205.5	P05496
ATP5MC1	ENST00000938823.1		c.41T>G	p.Ile14Ser	missense splice_region	Exon 3 of 6	ENSP00000608882.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

0.11

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.76

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.83

MutationAssessor

Pathogenic

2.9

PhyloP100

6.1

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.2

REVEL

Benign

0.21

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.10

Vest4

0.75

MutPred

0.61

Gain of disorder (P = 0.0216)

MVP

0.40

MPC

0.91

ClinPred

0.95

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.18

dbscSNV1_RF

Benign

0.35

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: -1

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over