Variant 9-111372480-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001364929.1(ECPAS):c.4477G>A(p.Glu1493Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000967 in 1,613,686 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

ECPAS
NM_001364929.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22295949).

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECPAS	NM_001364929.1 linkuse as main transcript	c.4477G>A	p.Glu1493Lys	missense_variant	42/50	ENST00000684092.1	NP_001351858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ECPAS	ENST00000684092.1 linkuse as main transcript	c.4477G>A	p.Glu1493Lys	missense_variant	42/50		NM_001364929.1	ENSP00000507419	P4
ECPAS	ENST00000259335.8 linkuse as main transcript	c.5011G>A	p.Glu1671Lys	missense_variant	43/51	1		ENSP00000259335
ECPAS	ENST00000338205.9 linkuse as main transcript	c.4477G>A	p.Glu1493Lys	missense_variant	41/49	5		ENSP00000339889	A1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000522

AC:

AN:

248878

Hom.:

AF XY:

0.0000593

AC XY:

AN XY:

135010

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000798

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

149

AN:

1461488

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000494

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000497

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 28, 2021

The c.5011G>A (p.E1671K) alteration is located in exon 43 (coding exon 43) of the KIAA0368 gene. This alteration results from a G to A substitution at nucleotide position 5011, causing the glutamic acid (E) at amino acid position 1671 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.90

N;N

REVEL

Benign

0.12

Sift

Benign

0.17

T;T

Sift4G

Benign

0.51

T;T

Vest4

0.48

MutPred

0.28

.;Gain of ubiquitination at E1671 (P = 0.0198);

MVP

0.19

MPC

0.31

ClinPred

0.16

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.50

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