20-59030494-T-A

Position:

• chr20-59030494-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000243997.8(ATP5F1E):​c.33-65A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,596,180 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00061 (8 hom.)
• Consequence: ATP5F1E ENST00000243997.8 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.883

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=-0.84).
• BP6: Variant 20-59030494-T-A is Benign according to our data. Variant chr20-59030494-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 677602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00561 (854/152344) while in subpopulation AFR AF= 0.0197 (818/41570). AF 95% confidence interval is 0.0186. There are 3 homozygotes in gnomad4. There are 413 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP5F1E	NM_006886.4	c.33-65A>T		intron_variant		ENST00000243997.8	NP_008817.1
SLMO2-ATP5E	NR_037930.1	n.478-65A>T		intron_variant, non_coding_transcript_variant
SLMO2-ATP5E	NR_037929.1	n.737-65A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP5F1E	ENST00000243997.8	c.33-65A>T		intron_variant		1	NM_006886.4	ENSP00000243997	P1
ATP5F1E	ENST00000395659.1	c.33-65A>T		intron_variant		1		ENSP00000379019	P1
ATP5F1E	ENST00000395663.1	c.33-65A>T		intron_variant		2		ENSP00000379023	P1

Frequencies

GnomAD3 genomes AF: 0.00561 AC: 854 AN: 152226 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000613 AC: 885 AN: 1443836 Hom.: 8 AF XY: 0.000527 AC XY: 379 AN XY: 719148

Gnomad4 AFR exome AF: 0.0213

Gnomad4 AMR exome AF: 0.000809

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000585

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000546

Gnomad4 OTH exome AF: 0.00128

GnomAD4 genome AF: 0.00561 AC: 854 AN: 152344 Hom.: 3 Cov.: 33 AF XY: 0.00554 AC XY: 413 AN XY: 74502

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00402 Hom.: 0

Bravo AF: 0.00636

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely 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	-0.84
CADD	Benign	0.57
DANN	Benign	0.72

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: rs78735620; hg19: chr20-57605549;