10-7802372-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001001973.3(ATP5F1C):c.740C>T(p.Thr247Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ATP5F1C
NM_001001973.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99

Variant links:

Genes affected

ATP5F1C (HGNC:833): (ATP synthase F1 subunit gamma) 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 consists of three main subunits (a, b, c). This gene encodes the gamma subunit of the catalytic core. Alternatively spliced transcript variants encoding different isoforms have been identified. This gene also has a pseudogene on chromosome 14. [provided by RefSeq, Jul 2008]

ATP5F1C links:

LOC105376392 (HGNC:):

LOC105376392 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5F1C	NM_001001973.3 link	c.740C>T	p.Thr247Ile	missense_variant	Exon 7 of 10	ENST00000356708.12	NP_001001973.1	P36542-1Q8TAS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5F1C	ENST00000356708.12 link	c.740C>T	p.Thr247Ile	missense_variant	Exon 7 of 10	1	NM_001001973.3	ENSP00000349142.7		P36542-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251168

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.740C>T (p.T247I) alteration is located in exon 7 (coding exon 7) of the ATP5C1 gene. This alteration results from a C to T substitution at nucleotide position 740, causing the threonine (T) at amino acid position 247 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.31

Sift

Benign

0.057

T;D

Sift4G

Uncertain

0.041

D;D

Polyphen

0.52

P;.

Vest4

0.87

MutPred

0.81

Loss of ubiquitination at K243 (P = 0.0367);Loss of ubiquitination at K243 (P = 0.0367);

MVP

0.62

MPC

0.53

ClinPred

0.83

GERP RS

5.5

Varity_R

0.19

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over