rs3761326

Variant names:

• chr21-25733821-T-A
• rs3761326
• NM_001003703.2:c.-8+1032A>T

Variant summary

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

The NM_001003701.2(ATP5PF):​c.17+1118A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,130 control chromosomes in the GnomAD database, including 8,490 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 0.29 (8490 hom., cov: 32)
• Consequence: ATP5PF NM_001003701.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003701.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5PF	NM_001003703.2	MANE Select	c.-8+1032A>T		intron	N/A	NP_001003703.1
	ATP5PF	NM_001003701.2		c.17+1118A>T		intron	N/A	NP_001003701.1
	ATP5PF	NM_001003696.2		c.-8+1494A>T		intron	N/A	NP_001003696.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5PF	ENST00000284971.8	TSL:1 MANE Select	c.-8+1032A>T		intron	N/A	ENSP00000284971.3
	ATP5PF	ENST00000400093.3	TSL:1	c.-8+1168A>T		intron	N/A	ENSP00000382965.3
	ATP5PF	ENST00000400099.5	TSL:5	c.-8+1168A>T		intron	N/A	ENSP00000382971.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44305 AN: 152012 Hom.: 8449 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.292 AC: 44393 AN: 152130 Hom.: 8490 Cov.: 32 AF XY: 0.292 AC XY: 21701 AN XY: 74396

African (AFR) AF: 0.543 AC: 22525 AN: 41466

American (AMR) AF: 0.250 AC: 3816 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1800 AN: 5186

South Asian (SAS) AF: 0.245 AC: 1185 AN: 4828

European-Finnish (FIN) AF: 0.186 AC: 1969 AN: 10606

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11770 AN: 67978

Other (OTH) AF: 0.275 AC: 581 AN: 2112

Alfa AF: 0.237 Hom.: 708

Bravo AF: 0.308

Asia WGS AF: 0.341 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.42
PhyloP100		-0.39
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: rs3761326; hg19: chr21-27106132;