20-59030592-C-T

Position:

• chr20-59030592-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006886.4(ATP5F1E):​c.33-163G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 152,136 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0068 (12 hom., cov: 33)
• Consequence: ATP5F1E NM_006886.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0670

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-59030592-C-T is Benign according to our data. Variant chr20-59030592-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1320592.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00679 (1033/152136) while in subpopulation AFR AF= 0.0234 (973/41494). AF 95% confidence interval is 0.0222. There are 12 homozygotes in gnomad4. There are 497 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP5F1E	NM_006886.4	c.33-163G>A		intron_variant		ENST00000243997.8	NP_008817.1
SLMO2-ATP5E	NR_037929.1	n.737-163G>A		intron_variant
SLMO2-ATP5E	NR_037930.1	n.478-163G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP5F1E	ENST00000243997.8	c.33-163G>A		intron_variant		1	NM_006886.4	ENSP00000243997.3
ATP5F1E	ENST00000395659.1	c.33-163G>A		intron_variant		1		ENSP00000379019.1
ATP5F1E	ENST00000395663.1	c.33-163G>A		intron_variant		2		ENSP00000379023.1

Frequencies

GnomAD3 genomes AF: 0.00679 AC: 1032 AN: 152018 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00526

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

GnomAD4 genome AF: 0.00679 AC: 1033 AN: 152136 Hom.: 12 Cov.: 33 AF XY: 0.00668 AC XY: 497 AN XY: 74376

Gnomad4 AFR AF: 0.0234

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00527 Hom.: 1

Bravo AF: 0.00791

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.60

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: rs77416814; hg19: chr20-57605647;