9-111362043-T-C

Variant names:

• chr9-111362043-T-C
• rs2098113894
• NM_001364929.1:c.5507A>G

Variant summary

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

The NM_001364929.1(ECPAS):​c.5507A>G​(p.Glu1836Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,208 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ECPAS NM_001364929.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51

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=0.21336713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECPAS	NM_001364929.1	c.5507A>G	p.Glu1836Gly	missense_variant	Exon 50 of 50	ENST00000684092.1	NP_001351858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECPAS	ENST00000684092.1	c.5507A>G	p.Glu1836Gly	missense_variant	Exon 50 of 50		NM_001364929.1	ENSP00000507419.1
ECPAS	ENST00000259335.8	c.6041A>G	p.Glu2014Gly	missense_variant	Exon 51 of 51	1		ENSP00000259335.4
ECPAS	ENST00000338205.9	c.5507A>G	p.Glu1836Gly	missense_variant	Exon 49 of 49	5		ENSP00000339889.5
ECPAS	ENST00000374383.1	c.416A>G	p.Glu139Gly	missense_variant	Exon 4 of 4	2		ENSP00000363504.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460208 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726374

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.6041A>G (p.E2014G) alteration is located in exon 51 (coding exon 51) of the KIAA0368 gene. This alteration results from a A to G substitution at nucleotide position 6041, causing the glutamic acid (E) at amino acid position 2014 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	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	.;.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	.;D;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.75	T
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	N;N;.
REVEL	Benign	0.14
Sift	Uncertain	0.023	D;D;.
Sift4G	Benign	0.076	T;D;D
Vest4		0.27
MutPred		0.17		.;Gain of loop (P = 0.0013);.;
MVP		0.14
MPC		0.39
ClinPred		0.90	D
GERP RS		5.9
gMVP		0.15

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: rs2098113894; hg19: chr9-114124323;