20-59032205-G-A

Position:

• chr20-59032205-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000243997.8(ATP5F1E):​c.32+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,573,664 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0012 (7 hom.)
• Consequence: ATP5F1E ENST00000243997.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.19

Genes affected

ATP5F1E (HGNC:838): (ATP synthase F1 subunit epsilon) 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 epsilon subunit of the catalytic core. Two pseudogenes of this gene are located on chromosomes 4 and 13. Read-through transcripts that include exons from this gene are expressed from the upstream gene SLMO2.[provided by RefSeq, Mar 2011]

SLMO2-ATP5E (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 20-59032205-G-A is Benign according to our data. Variant chr20-59032205-G-A is described in ClinVar as [Benign]. Clinvar id is 136462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP5F1E	NM_006886.4	c.32+15C>T		intron_variant		ENST00000243997.8	NP_008817.1
SLMO2-ATP5E	NR_037930.1	n.478-1776C>T		intron_variant, non_coding_transcript_variant
SLMO2-ATP5E	NR_037929.1	n.737-1776C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP5F1E	ENST00000243997.8	c.32+15C>T		intron_variant		1	NM_006886.4	ENSP00000243997	P1
ATP5F1E	ENST00000395659.1	c.32+15C>T		intron_variant		1		ENSP00000379019	P1
ATP5F1E	ENST00000395663.1	c.32+15C>T		intron_variant		2		ENSP00000379023	P1

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 221 AN: 152220 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.00182

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00147 AC: 274 AN: 186326 Hom.: 2 AF XY: 0.00170 AC XY: 171 AN XY: 100860

Gnomad AFR exome AF: 0.000191

Gnomad AMR exome AF: 0.000961

Gnomad ASJ exome AF: 0.00146

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00250

Gnomad FIN exome AF: 0.000300

Gnomad NFE exome AF: 0.00184

Gnomad OTH exome AF: 0.00384

GnomAD4 exome AF: 0.00124 AC: 1767 AN: 1421326 Hom.: 7 Cov.: 31 AF XY: 0.00131 AC XY: 925 AN XY: 703462

Gnomad4 AFR exome AF: 0.000183

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.00205

Gnomad4 EAS exome AF: 0.0000265

Gnomad4 SAS exome AF: 0.00217

Gnomad4 FIN exome AF: 0.000575

Gnomad4 NFE exome AF: 0.00120

Gnomad4 OTH exome AF: 0.00178

GnomAD4 genome AF: 0.00145 AC: 221 AN: 152338 Hom.: 1 Cov.: 34 AF XY: 0.00158 AC XY: 118 AN XY: 74492

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.00346

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00182

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00176 Hom.: 1

Bravo AF: 0.00135

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 14, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Uncertain	0.99

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: rs45545036; hg19: chr20-57607260;