9-111362104-T-A

Position:

• chr9-111362104-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364929.1(ECPAS):​c.5446A>T​(p.Met1816Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECPAS NM_001364929.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08206239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECPAS	NM_001364929.1	c.5446A>T	p.Met1816Leu	missense_variant	50/50	ENST00000684092.1	NP_001351858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECPAS	ENST00000684092.1	c.5446A>T	p.Met1816Leu	missense_variant	50/50		NM_001364929.1	ENSP00000507419	P4
ECPAS	ENST00000259335.8	c.5980A>T	p.Met1994Leu	missense_variant	51/51	1		ENSP00000259335
ECPAS	ENST00000338205.9	c.5446A>T	p.Met1816Leu	missense_variant	49/49	5		ENSP00000339889	A1
ECPAS	ENST00000374383.1	c.406-51A>T		intron_variant		2		ENSP00000363504

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.5980A>T (p.M1994L) alteration is located in exon 51 (coding exon 51) of the KIAA0368 gene. This alteration results from a A to T substitution at nucleotide position 5980, causing the methionine (M) at amino acid position 1994 to be replaced by a leucine (L). 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	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.65
Eigen	Benign	-0.22
Eigen_PC	Benign	0.020
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.32	N;N
REVEL	Benign	0.079
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.24
MutPred		0.11		.;Gain of catalytic residue at M1994 (P = 0.0533);
MVP		0.12
MPC		0.15
ClinPred		0.92	D
GERP RS		5.9
gMVP		0.22

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

Other links and lift over

dbSNP: rs201238185; hg19: chr9-114124384;