20-50153533-AG-A

Position:

• chr20-50153533-AG-A

Variant summary

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

The NM_199129.4(PEDS1):​c.104delC​(p.Ala35fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PEDS1 NM_199129.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06

Genes affected

PEDS1 (HGNC:16735): (plasmanylethanolamine desaturase 1) Co-transcription of this gene and the neighboring downstream gene (ubiquitin-conjugating enzyme E2 variant 1) generates a rare read-through transcript, which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. The protein encoded by this individual gene lacks a UEV1 domain but includes three transmembrane regions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2009]

PEDS1-UBE2V1 (HGNC:33521): (PEDS1-UBE2V1 readthrough) The TMEM189-UEV mRNA is an infrequent but naturally occurring read-through transcript of the neighboring TMEM189 and UBE2V1 genes. Ubiquitin-conjugating E2 enzyme variant proteins constitute a distinct subfamily within the E2 protein family. They have sequence similarity to other ubiquitin-conjugating enzymes but lack the conserved cysteine residue that is critical for the catalytic activity of E2s. The protein produced by this transcript has UEV1 B domains but the protein is localized to the cytoplasm rather than to the nucleus. The significance of this read-through mRNA and the function of its protein product has not yet been determined. [provided by RefSeq, Oct 2010]

PEDS1 (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/exons	MANE	Protein	UniProt
PEDS1	NM_199129.4	c.104delC	p.Ala35fs	frameshift_variant	1/6	ENST00000371652.9	NP_954580.2
PEDS1-UBE2V1	NM_199203.3	c.104delC	p.Ala35fs	frameshift_variant	1/8		NP_954673.2
PEDS1	NM_001162505.2	c.104delC	p.Ala35fs	frameshift_variant	1/6		NP_001155977.2
PEDS1	NR_027889.2	n.190delC		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEDS1	ENST00000371652.9	c.104delC	p.Ala35fs	frameshift_variant	1/6	1	NM_199129.4	ENSP00000360715.4
PEDS1-UBE2V1	ENST00000341698.2	c.104delC	p.Ala35fs	frameshift_variant	1/8	1		ENSP00000344166.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Hadassah Hebrew University Medical Center

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Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-48770070;