9-111370763-C-T

Variant names:

• chr9-111370763-C-T
• rs749021991
• NM_001364929.1:c.4740G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001364929.1(ECPAS):​c.4740G>A​(p.Glu1580Glu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECPAS NM_001364929.1 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 1 publications found

Genes affected

ECPAS (HGNC:29020): (Ecm29 proteasome adaptor and scaffold) Enables proteasome binding activity. Involved in ubiquitin-dependent ERAD pathway. Located in several cellular components, including centrosome; cytoplasmic vesicle; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=1.01 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364929.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECPAS	NM_001364929.1	MANE Select	c.4740G>A	p.Glu1580Glu	splice_region synonymous	Exon 44 of 50	NP_001351858.1	Q5VYK3-2
	ECPAS	NM_001364931.1		c.4758G>A	p.Glu1586Glu	splice_region synonymous	Exon 43 of 49	NP_001351860.1	Q5VYK3-1
	ECPAS	NM_001363756.2		c.4740G>A	p.Glu1580Glu	splice_region synonymous	Exon 43 of 49	NP_001350685.1	A0AAA9X0G7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECPAS	ENST00000684092.1	MANE Select	c.4740G>A	p.Glu1580Glu	splice_region synonymous	Exon 44 of 50	ENSP00000507419.1	Q5VYK3-2
	ECPAS	ENST00000259335.8	TSL:1	c.5274G>A	p.Glu1758Glu	splice_region synonymous	Exon 45 of 51	ENSP00000259335.4	J3KN16
	ECPAS	ENST00000338205.9	TSL:5	c.4740G>A	p.Glu1580Glu	splice_region synonymous	Exon 43 of 49	ENSP00000339889.5	A0AAA9X0G7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.3
DANN	Benign	0.54
PhyloP100		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs749021991; hg19: chr9-114133043;