Genetic Variant NM_005175.3:c.-23T>C (chr17-48892897-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.918

Publications

34 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: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
ATP5MC1	NM_005175.3 link	c.-23T>C	5_prime_UTR_variant	Exon 1 of 5	ENST00000393366.7	NP_005166.1	P05496Q6FIH7
ATP5MC1	NM_001002027.2 link	c.-10+57T>C	intron_variant	Intron 1 of 4		NP_001002027.1	P05496Q6FIH7
LOC105371814	NR_135674.1 link	n.46-220A>G	intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5MC1	ENST00000393366.7 link	c.-23T>C		5_prime_UTR_variant	Exon 1 of 5	1	NM_005175.3	ENSP00000377033.2		P05496

Frequencies

GnomAD3 genomes

AF:

0.642

AC:

97224

AN:

151384

Hom.:

31900

Cov.:

show subpopulations

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.:

AF XY:

0.711

AC XY:

2281

AN XY:

3206

show subpopulations

African (AFR)

AF:

0.542

AC:

AN:

American (AMR)

AF:

0.549

AC:

167

AN:

304

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

AN:

East Asian (EAS)

AF:

0.827

AC:

AN:

110

South Asian (SAS)

AF:

0.713

AC:

784

AN:

1100

European-Finnish (FIN)

AF:

0.736

AC:

190

AN:

258

Middle Eastern (MID)

AF:

0.571

AC:

AN:

European-Non Finnish (NFE)

AF:

0.729

AC:

2108

AN:

2890

Other (OTH)

AF:

0.726

AC:

138

AN:

190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

144

192

240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.642

AC:

97261

AN:

151502

Hom.:

31906

Cov.:

AF XY:

0.642

AC XY:

47518

AN XY:

73982

show subpopulations

African (AFR)

AF:

0.529

AC:

21790

AN:

41212

American (AMR)

AF:

0.547

AC:

8327

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

2037

AN:

3464

East Asian (EAS)

AF:

0.840

AC:

4292

AN:

5112

South Asian (SAS)

AF:

0.726

AC:

3483

AN:

4800

European-Finnish (FIN)

AF:

0.740

AC:

7767

AN:

10502

Middle Eastern (MID)

AF:

0.616

AC:

181

AN:

294

European-Non Finnish (NFE)

AF:

0.698

AC:

47358

AN:

67896

Other (OTH)

AF:

0.652

AC:

1372

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1723

3446

5170

6893

8616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.673

Hom.:

35922

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

(source)

DANN

Benign

0.88

PhyloP100

0.92

PromoterAI

-0.064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over