9-111370547-T-C

Variant names:

• chr9-111370547-T-C
• NM_001364929.1:c.4862A>G

Variant summary

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

The NM_001364929.1(ECPAS):​c.4862A>G​(p.Glu1621Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ECPAS NM_001364929.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.43

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECPAS	NM_001364929.1	c.4862A>G	p.Glu1621Gly	missense_variant	Exon 45 of 50	ENST00000684092.1	NP_001351858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECPAS	ENST00000684092.1	c.4862A>G	p.Glu1621Gly	missense_variant	Exon 45 of 50		NM_001364929.1	ENSP00000507419.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5396A>G (p.E1799G) alteration is located in exon 46 (coding exon 46) of the KIAA0368 gene. This alteration results from a A to G substitution at nucleotide position 5396, causing the glutamic acid (E) at amino acid position 1799 to be replaced by a glycine (G). 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	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;.;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.51	T
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.7	D;D;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.0040	D;D;.
Sift4G	Uncertain	0.0040	D;D;D
Vest4		0.34
MutPred		0.45		.;Loss of stability (P = 0.0433);.;
MVP		0.54
MPC		0.43
ClinPred		0.98	D
GERP RS		5.8
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-114132827;