ATP5F1C p.Ser116Arg

Variant names:

• chr10-7799112-A-C
• NM_001001973.3:c.346A>C
• ATP5F1C p.Ser116Arg

Your query was ambiguous. Multiple possible variants found:

• chr10-7799112-A-C
• chr10-7799114-C-A
• chr10-7799114-C-G
• chr10-7799112-AGC-CGT
• chr10-7799112-AGC-CGA
• chr10-7799112-AGC-CGG

Variant summary

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

The NM_001001973.3(ATP5F1C):​c.346A>C​(p.Ser116Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATP5F1C NM_001001973.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.88
• Publications: 0 publications found

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]

ENSG00000305746 (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 (MetaRNN=0.17051536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001973.3. 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
	ATP5F1C	NM_001001973.3	MANE Select	c.346A>C	p.Ser116Arg	missense	Exon 4 of 10	NP_001001973.1	P36542-1
	ATP5F1C	NM_005174.4		c.346A>C	p.Ser116Arg	missense	Exon 4 of 9	NP_005165.1	P36542-2
	ATP5F1C	NM_001320886.2		c.205A>C	p.Ser69Arg	missense	Exon 3 of 9	NP_001307815.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5F1C	ENST00000356708.12	TSL:1 MANE Select	c.346A>C	p.Ser116Arg	missense	Exon 4 of 10	ENSP00000349142.7	P36542-1
	ATP5F1C	ENST00000335698.4	TSL:1	c.346A>C	p.Ser116Arg	missense	Exon 4 of 9	ENSP00000338568.4	P36542-2
	ATP5F1C	ENST00000864428.1		c.346A>C	p.Ser116Arg	missense	Exon 4 of 11	ENSP00000534487.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.34
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L
PhyloP100		5.9
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.26
Sift	Benign	0.66	T
Sift4G	Benign	0.65	T
Varity_R		0.088
gMVP		0.50
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-7841075;