NM_001364929.1:c.5507A>C

Variant names:

• chr9-111362043-T-G
• rs2098113894
• NM_001364929.1:c.5507A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364929.1(ECPAS):​c.5507A>C​(p.Glu1836Ala) variant causes a missense 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1836G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECPAS NM_001364929.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17525169).

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.5507A>C	p.Glu1836Ala	missense	Exon 50 of 50	NP_001351858.1	Q5VYK3-2
	ECPAS	NM_001364931.1		c.5525A>C	p.Glu1842Ala	missense	Exon 49 of 49	NP_001351860.1	Q5VYK3-1
	ECPAS	NM_001363756.2		c.5507A>C	p.Glu1836Ala	missense	Exon 49 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.5507A>C	p.Glu1836Ala	missense	Exon 50 of 50	ENSP00000507419.1	Q5VYK3-2
	ECPAS	ENST00000259335.8	TSL:1	c.6041A>C	p.Glu2014Ala	missense	Exon 51 of 51	ENSP00000259335.4	J3KN16
	ECPAS	ENST00000338205.9	TSL:5	c.5507A>C	p.Glu1836Ala	missense	Exon 49 of 49	ENSP00000339889.5	A0AAA9X0G7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.84	T
PhyloP100		3.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Benign	0.051	T
Sift4G	Benign	0.16	T
Vest4		0.30
MutPred		0.10		Gain of MoRF binding (P = 0.0302)
MVP		0.13
MPC		0.26
ClinPred		0.74	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.15
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs2098113894; hg19: chr9-114124323; COSMIC: COSV52203284; COSMIC: COSV52203284;