rs4842

Variant names:

• chr21-33909117-T-C
• rs4842
• NM_001697.3:c.293A>G

Variant summary

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

The NM_001697.3(ATP5PO):​c.293A>G​(p.Lys98Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0895 in 1,612,302 control chromosomes in the GnomAD database, including 7,003 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.088 (638 hom., cov: 33)
  • Exomes 𝑓: 0.090 (6365 hom.)
• Consequence: ATP5PO NM_001697.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85
• Publications: 22 publications found

Genes affected

ATP5PO (HGNC:850): (ATP synthase peripheral stalk subunit OSCP) The protein encoded by this gene is a component of the F-type ATPase found in the mitochondrial matrix. F-type ATPases are composed of a catalytic core and a membrane proton channel. The encoded protein appears to be part of the connector linking these two components and may be involved in transmission of conformational changes or proton conductance. [provided by RefSeq, Jul 2008]

ENSG00000249209 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022473037).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001697.3. 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
	ATP5PO	NM_001697.3	MANE Select	c.293A>G	p.Lys98Arg	missense	Exon 4 of 7	NP_001688.1	P48047

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5PO	ENST00000290299.7	TSL:1 MANE Select	c.293A>G	p.Lys98Arg	missense	Exon 4 of 7	ENSP00000290299.2	P48047
	ENSG00000249209	ENST00000429238.2	TSL:5	c.293A>G	p.Lys98Arg	missense	Exon 5 of 8	ENSP00000394107.2	H7C0C1
	ATP5PO	ENST00000892991.1		c.293A>G	p.Lys98Arg	missense	Exon 4 of 7	ENSP00000563050.1

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13337 AN: 152186 Hom.: 638 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.0947

GnomAD2 exomes AF: 0.0794 AC: 19969 AN: 251386 AF XY: 0.0813

Gnomad AFR exome AF: 0.0991

Gnomad AMR exome AF: 0.0452

Gnomad ASJ exome AF: 0.119

Gnomad EAS exome AF: 0.0163

Gnomad FIN exome AF: 0.0539

Gnomad NFE exome AF: 0.0974

Gnomad OTH exome AF: 0.0833

GnomAD4 exome AF: 0.0896 AC: 130885 AN: 1459998 Hom.: 6365 Cov.: 33 AF XY: 0.0896 AC XY: 65074 AN XY: 726430

African (AFR) AF: 0.101 AC: 3392 AN: 33424

American (AMR) AF: 0.0475 AC: 2124 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 3024 AN: 26122

East Asian (EAS) AF: 0.0122 AC: 483 AN: 39698

South Asian (SAS) AF: 0.0844 AC: 7274 AN: 86220

European-Finnish (FIN) AF: 0.0535 AC: 2859 AN: 53412

Middle Eastern (MID) AF: 0.0653 AC: 376 AN: 5762

European-Non Finnish (NFE) AF: 0.0957 AC: 106227 AN: 1110318

Other (OTH) AF: 0.0849 AC: 5126 AN: 60342

GnomAD4 genome AF: 0.0877 AC: 13356 AN: 152304 Hom.: 638 Cov.: 33 AF XY: 0.0841 AC XY: 6261 AN XY: 74490

African (AFR) AF: 0.102 AC: 4239 AN: 41564

American (AMR) AF: 0.0617 AC: 945 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3472

East Asian (EAS) AF: 0.0164 AC: 85 AN: 5186

South Asian (SAS) AF: 0.0816 AC: 394 AN: 4828

European-Finnish (FIN) AF: 0.0523 AC: 555 AN: 10612

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0938 AC: 6377 AN: 68020

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.0929 Hom.: 2441

Bravo AF: 0.0895

Asia WGS AF: 0.0510 AC: 176 AN: 3478

EpiCase AF: 0.0938

EpiControl AF: 0.0933

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
PhyloP100		3.8
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.50
Mutation Taster		=89/11	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

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

Other links and lift over

dbSNP: rs4842; hg19: chr21-35281421; COSMIC: COSV51708983; COSMIC: COSV51708983;