20-59031916-A-G

Position:

• chr20-59031916-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000243997.8(ATP5F1E):​c.32+304T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,236 control chromosomes in the GnomAD database, including 4,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.24 (4344 hom., cov: 34)
• Consequence: ATP5F1E ENST00000243997.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.884

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-59031916-A-G is Benign according to our data. Variant chr20-59031916-A-G is described in ClinVar as [Benign]. Clinvar id is 683340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP5F1E	NM_006886.4	c.32+304T>C		intron_variant		ENST00000243997.8	NP_008817.1
SLMO2-ATP5E	NR_037930.1	n.478-1487T>C		intron_variant, non_coding_transcript_variant
SLMO2-ATP5E	NR_037929.1	n.737-1487T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP5F1E	ENST00000243997.8	c.32+304T>C		intron_variant		1	NM_006886.4	ENSP00000243997	P1
ATP5F1E	ENST00000395659.1	c.32+304T>C		intron_variant		1		ENSP00000379019	P1
ATP5F1E	ENST00000395663.1	c.32+304T>C		intron_variant		2		ENSP00000379023	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35752 AN: 152118 Hom.: 4338 Cov.: 34

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.235 AC: 35788 AN: 152236 Hom.: 4344 Cov.: 34 AF XY: 0.240 AC XY: 17843 AN XY: 74450

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.225

Alfa AF: 0.225 Hom.: 1190

Bravo AF: 0.225

Asia WGS AF: 0.149 AC: 520 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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	-0.83
CADD	Benign	1.5
DANN	Benign	0.42

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: rs151354; hg19: chr20-57606971;