chr9-111369155-C-T

Variant names:

• chr9-111369155-C-T
• NM_001364929.1:c.4993G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4 BS2

The NM_001364929.1(ECPAS):​c.4993G>A​(p.Gly1665Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000349 in 1,434,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: ECPAS NM_001364929.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91
• 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: 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 (MetaRNN=0.28640622).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.4993G>A	p.Gly1665Arg	missense	Exon 46 of 50	NP_001351858.1	Q5VYK3-2
	ECPAS	NM_001364931.1		c.5011G>A	p.Gly1671Arg	missense	Exon 45 of 49	NP_001351860.1	Q5VYK3-1
	ECPAS	NM_001363756.2		c.4993G>A	p.Gly1665Arg	missense	Exon 45 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.4993G>A	p.Gly1665Arg	missense	Exon 46 of 50	ENSP00000507419.1	Q5VYK3-2
	ECPAS	ENST00000259335.8	TSL:1	c.5527G>A	p.Gly1843Arg	missense	Exon 47 of 51	ENSP00000259335.4	J3KN16
	ECPAS	ENST00000338205.9	TSL:5	c.4993G>A	p.Gly1665Arg	missense	Exon 45 of 49	ENSP00000339889.5	A0AAA9X0G7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000349 AC: 5 AN: 1434168 Hom.: 0 Cov.: 30 AF XY: 0.00000561 AC XY: 4 AN XY: 713380

African (AFR) AF: 0.00 AC: 0 AN: 31204

American (AMR) AF: 0.00 AC: 0 AN: 37078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24938

East Asian (EAS) AF: 0.00 AC: 0 AN: 38490

South Asian (SAS) AF: 0.00 AC: 0 AN: 81390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.00000453 AC: 5 AN: 1103350

Other (OTH) AF: 0.00 AC: 0 AN: 59112

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Benign	0.0035
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.77	T
PhyloP100		1.9
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.15
Sift	Benign	0.26	T
Sift4G	Benign	0.34	T
Vest4		0.53
MutPred		0.28		Gain of catalytic residue at G1843 (P = 0.0112)
MVP		0.13
MPC		0.28
ClinPred		0.56	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.32
Mutation Taster		=68/32	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

hg19: chr9-114131435;