10-7800426-A-T

Variant names:

• chr10-7800426-A-T
• rs1244426
• NM_001001973.3:c.637+335A>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.637+335A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 150,218 control chromosomes in the GnomAD database, including 9,134 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 0.35 (9134 hom., cov: 30)
• Consequence: ATP5F1C NM_001001973.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5F1C	NM_001001973.3	c.637+335A>T		intron_variant	Intron 6 of 9	ENST00000356708.12	NP_001001973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5F1C	ENST00000356708.12	c.637+335A>T		intron_variant	Intron 6 of 9	1	NM_001001973.3	ENSP00000349142.7

Frequencies

GnomAD3 genomes AF: 0.350 AC: 52511 AN: 150124 Hom.: 9134 Cov.: 30

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.328

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.350 AC: 52537 AN: 150218 Hom.: 9134 Cov.: 30 AF XY: 0.349 AC XY: 25582 AN XY: 73204

African (AFR) AF: 0.313 AC: 12793 AN: 40826

American (AMR) AF: 0.361 AC: 5448 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1240 AN: 3460

East Asian (EAS) AF: 0.244 AC: 1233 AN: 5050

South Asian (SAS) AF: 0.437 AC: 2085 AN: 4766

European-Finnish (FIN) AF: 0.361 AC: 3641 AN: 10096

Middle Eastern (MID) AF: 0.350 AC: 96 AN: 274

European-Non Finnish (NFE) AF: 0.371 AC: 25088 AN: 67660

Other (OTH) AF: 0.329 AC: 686 AN: 2082

Alfa AF: 0.350 Hom.: 1153

Bravo AF: 0.341

Asia WGS AF: 0.369 AC: 1285 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.73
PhyloP100		0.38
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: rs1244426; hg19: chr10-7842389;