Variant 9-111371662-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001364929.1(ECPAS):c.4696G>A(p.Ala1566Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,692 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 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ECPAS
NM_001364929.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.41800132).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECPAS	NM_001364929.1 linkuse as main transcript	c.4696G>A	p.Ala1566Thr	missense_variant	43/50	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.4696G>A	p.Ala1566Thr	missense_variant	43/50		NM_001364929.1	ENSP00000507419	P4
ECPAS	ENST00000259335.8 linkuse as main transcript	c.5230G>A	p.Ala1744Thr	missense_variant	44/51	1		ENSP00000259335
ECPAS	ENST00000338205.9 linkuse as main transcript	c.4696G>A	p.Ala1566Thr	missense_variant	42/49	5		ENSP00000339889	A1
ECPAS	ENST00000374383.1 linkuse as main transcript	c.127G>A	p.Ala43Thr	missense_variant	1/4	2		ENSP00000363504

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249036

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135084

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461580

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Apr 16, 2024

The c.5230G>A (p.A1744T) alteration is located in exon 44 (coding exon 44) of the KIAA0368 gene. This alteration results from a G to A substitution at nucleotide position 5230, causing the alanine (A) at amino acid position 1744 to be replaced by a threonine (T). 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

-0.035

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.034

.;.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

.;D;D

M_CAP

Benign

0.053

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-0.55

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.98

N;N;.

REVEL

Benign

0.24

Sift

Benign

0.22

T;T;.

Sift4G

Benign

0.18

T;T;D

Vest4

0.75

MutPred

0.40

.;Gain of catalytic residue at A1744 (P = 0.1102);.;

MVP

0.49

MPC

0.53

ClinPred

0.47

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.39

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