rs2829887

chr21-25731303-C-Tchr21-25731303-C-Achr21-25731303-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003703.2(ATP5PF):c.-7-1502G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,104 control chromosomes in the GnomAD database, including 10,491 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 0.34 (10491 hom., cov: 32)
• Consequence: ATP5PF NM_001003703.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

Genes affected

ATP5PF (HGNC:847): (ATP synthase peripheral stalk subunit F6) Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. It is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, which comprises the proton channel. The F1 complex consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled in a ratio of 3 alpha, 3 beta, and a single representative of the other 3. The Fo complex has nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the F6 subunit of the Fo complex. The F6 subunit is required for F1 and Fo interactions. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. This gene has 1 or more pseudogenes. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP5PF	NM_001003703.2	c.-7-1502G>A		intron_variant		ENST00000284971.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP5PF	ENST00000284971.8	c.-7-1502G>A		intron_variant		1	NM_001003703.2	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51280 AN: 151986 Hom.: 10495 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.337 AC: 51274 AN: 152104 Hom.: 10491 Cov.: 32 AF XY: 0.337 AC XY: 25018 AN XY: 74342

Gnomad4 AFR AF: 0.0986

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.382

Alfa AF: 0.371 Hom.: 2704

Bravo AF: 0.326

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.7
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs2829887; hg19: chr21-27103614;