chr20-59032215-C-T

Variant names:

• chr20-59032215-C-T
• NM_006886.4:c.32+5G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006886.4(ATP5F1E):​c.32+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,428,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ATP5F1E NM_006886.4 splice_region, intron
• Scores: Splicing: ADA: 0.9988
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5F1E	NM_006886.4	c.32+5G>A		splice_region_variant, intron_variant	Intron 1 of 2	ENST00000243997.8	NP_008817.1
SLMO2-ATP5E	NR_037929.1	n.737-1786G>A		intron_variant	Intron 6 of 7
SLMO2-ATP5E	NR_037930.1	n.478-1786G>A		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5F1E	ENST00000243997.8	c.32+5G>A		splice_region_variant, intron_variant	Intron 1 of 2	1	NM_006886.4	ENSP00000243997.3
ATP5F1E	ENST00000395659.1	c.32+5G>A		splice_region_variant, intron_variant	Intron 1 of 1	1		ENSP00000379019.1
ATP5F1E	ENST00000395663.1	c.32+5G>A		splice_region_variant, intron_variant	Intron 1 of 2	2		ENSP00000379023.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1428400 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 707544

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000255

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.83
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-57607270;