Genetic Variant ECPAS:p.Ala1701Val (chr9-111369046-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001364929.1(ECPAS):c.5102C>T(p.Ala1701Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,586,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ECPAS
NM_001364929.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05

Variant links:

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]

ECPAS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02463761).

BP6

Variant 9-111369046-G-A is Benign according to our data. Variant chr9-111369046-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3274427.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECPAS	NM_001364929.1 link	c.5102C>T	p.Ala1701Val	missense_variant	Exon 46 of 50	ENST00000684092.1	NP_001351858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECPAS	ENST00000684092.1 link	c.5102C>T	p.Ala1701Val	missense_variant	Exon 46 of 50		NM_001364929.1	ENSP00000507419.1		A0A804HJA4

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000720

AC:

AN:

222164

Hom.:

AF XY:

0.0000660

AC XY:

AN XY:

121302

show subpopulations

Gnomad AFR exome

AF:

0.000417

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000515

Gnomad SAS exome

AF:

0.0000789

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000223

AC:

AN:

1433910

Hom.:

Cov.:

AF XY:

0.0000182

AC XY:

AN XY:

713284

show subpopulations

Gnomad4 AFR exome

AF:

0.000383

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000156

Gnomad4 SAS exome

AF:

0.0000492

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000635

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000497

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 16, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.17

DANN

Benign

0.77

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.080

Sift

Benign

0.33

T;T

Sift4G

Benign

0.45

T;T

Vest4

0.068

MutPred

0.36

.;Loss of disorder (P = 0.0744);

MVP

0.33

MPC

0.16

ClinPred

0.010

GERP RS

-8.5

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

gMVP

0.043

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over