10-7796969-C-T

Variant names:

• chr10-7796969-C-T
• rs1244422
• NM_001001973.3:c.92-78C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001973.3(ATP5F1C):​c.92-78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,506,596 control chromosomes in the GnomAD database, including 144,285 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 0.44 (14706 hom., cov: 32)
  • Exomes 𝑓: 0.43 (129579 hom.)
• Consequence: ATP5F1C NM_001001973.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

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.92-78C>T		intron	N/A	NP_001001973.1	P36542-1
	ATP5F1C	NM_005174.4		c.92-78C>T		intron	N/A	NP_005165.1	P36542-2
	ATP5F1C	NM_001320886.2		c.-50-78C>T		intron	N/A	NP_001307815.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5F1C	ENST00000356708.12	TSL:1 MANE Select	c.92-78C>T		intron	N/A	ENSP00000349142.7	P36542-1
	ATP5F1C	ENST00000335698.4	TSL:1	c.92-78C>T		intron	N/A	ENSP00000338568.4	P36542-2
	ATP5F1C	ENST00000864428.1		c.92-78C>T		intron	N/A	ENSP00000534487.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66547 AN: 151920 Hom.: 14699 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.435 AC: 588631 AN: 1354560 Hom.: 129579 Cov.: 21 AF XY: 0.436 AC XY: 292243 AN XY: 669888

African (AFR) AF: 0.452 AC: 13535 AN: 29950

American (AMR) AF: 0.557 AC: 19634 AN: 35254

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 9468 AN: 22756

East Asian (EAS) AF: 0.326 AC: 12427 AN: 38154

South Asian (SAS) AF: 0.539 AC: 40323 AN: 74768

European-Finnish (FIN) AF: 0.367 AC: 18672 AN: 50810

Middle Eastern (MID) AF: 0.425 AC: 2098 AN: 4938

European-Non Finnish (NFE) AF: 0.430 AC: 447954 AN: 1041656

Other (OTH) AF: 0.436 AC: 24520 AN: 56274

GnomAD4 genome AF: 0.438 AC: 66592 AN: 152036 Hom.: 14706 Cov.: 32 AF XY: 0.437 AC XY: 32462 AN XY: 74330

African (AFR) AF: 0.449 AC: 18623 AN: 41456

American (AMR) AF: 0.492 AC: 7517 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1627 AN: 5170

South Asian (SAS) AF: 0.552 AC: 2663 AN: 4824

European-Finnish (FIN) AF: 0.378 AC: 3988 AN: 10562

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.434 AC: 29489 AN: 67960

Other (OTH) AF: 0.418 AC: 884 AN: 2114

Alfa AF: 0.429 Hom.: 38200

Bravo AF: 0.442

Asia WGS AF: 0.470 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.062
DANN	Benign	0.63
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1244422; hg19: chr10-7838932; COSMIC: COSV59621836; COSMIC: COSV59621836;