Variant 9-111372455-G-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.4502C>A(p.Thr1501Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ECPAS
NM_001364929.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

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=0.08942336).

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECPAS	NM_001364929.1 linkuse as main transcript	c.4502C>A	p.Thr1501Asn	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.4502C>A	p.Thr1501Asn	missense_variant	42/50		NM_001364929.1	ENSP00000507419	P4
ECPAS	ENST00000259335.8 linkuse as main transcript	c.5036C>A	p.Thr1679Asn	missense_variant	43/51	1		ENSP00000259335
ECPAS	ENST00000338205.9 linkuse as main transcript	c.4502C>A	p.Thr1501Asn	missense_variant	41/49	5		ENSP00000339889	A1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152180

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:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000563

AC:

AN:

248796

Hom.:

AF XY:

0.0000667

AC XY:

AN XY:

134964

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000779

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461460

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000414

AC:

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

Mar 22, 2023

The c.5036C>A (p.T1679N) alteration is located in exon 43 (coding exon 43) of the KIAA0368 gene. This alteration results from a C to A substitution at nucleotide position 5036, causing the threonine (T) at amino acid position 1679 to be replaced by an asparagine (N). 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

-0.41

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.015

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

.;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.54

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.78

N;N

REVEL

Benign

0.024

Sift

Benign

0.041

D;T

Sift4G

Benign

0.31

T;T

Vest4

0.38

MutPred

0.34

.;Gain of disorder (P = 0.1729);

MVP

0.20

MPC

0.30

ClinPred

0.11

GERP RS

5.9

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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