rs538430585

Variant names:

• chr9-111370601-T-C
• rs538430585
• NM_001364929.1:c.4808A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-111370601-T-C
• chr9-111370601-T-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001364929.1(ECPAS):​c.4808A>G​(p.Asn1603Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000509 in 1,611,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: ECPAS NM_001364929.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.149
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02297023).
• BP6: Variant 9-111370601-T-C is Benign according to our data. Variant chr9-111370601-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3087071.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 12 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.4808A>G	p.Asn1603Ser	missense	Exon 45 of 50	NP_001351858.1	Q5VYK3-2
	ECPAS	NM_001364931.1		c.4826A>G	p.Asn1609Ser	missense	Exon 44 of 49	NP_001351860.1	Q5VYK3-1
	ECPAS	NM_001363756.2		c.4808A>G	p.Asn1603Ser	missense	Exon 44 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.4808A>G	p.Asn1603Ser	missense	Exon 45 of 50	ENSP00000507419.1	Q5VYK3-2
	ECPAS	ENST00000259335.8	TSL:1	c.5342A>G	p.Asn1781Ser	missense	Exon 46 of 51	ENSP00000259335.4	J3KN16
	ECPAS	ENST00000338205.9	TSL:5	c.4808A>G	p.Asn1603Ser	missense	Exon 44 of 49	ENSP00000339889.5	A0AAA9X0G7

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000739 AC: 18 AN: 243690 AF XY: 0.0000681

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.0000889

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000998

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000480 AC: 70 AN: 1458856 Hom.: 0 Cov.: 32 AF XY: 0.0000496 AC XY: 36 AN XY: 725420

African (AFR) AF: 0.0000897 AC: 3 AN: 33448

American (AMR) AF: 0.0000452 AC: 2 AN: 44236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.000117 AC: 10 AN: 85644

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53306

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1110556

Other (OTH) AF: 0.0000498 AC: 3 AN: 60294

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74486

African (AFR) AF: 0.0000722 AC: 3 AN: 41572

American (AMR) AF: 0.000196 AC: 3 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000123 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000414 AC: 5

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.061
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.096
DANN	Benign	0.47
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.15
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.095
Sift	Benign	0.60	T
Sift4G	Benign	0.90	T
Vest4		0.071
MVP		0.16
MPC		0.13
ClinPred		0.014	T
GERP RS		-6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.055
Mutation Taster		=85/15	polymorphism

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: rs538430585; hg19: chr9-114132881; COSMIC: COSV107268002;