NM_001364929.1:c.4378A>C

Variant names:

• chr9-111372579-T-G
• rs142217155
• NM_001364929.1:c.4378A>C

Variant summary

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

The NM_001364929.1(ECPAS):​c.4378A>C​(p.Ile1460Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ECPAS NM_001364929.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.48

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=0.25244266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECPAS	NM_001364929.1	c.4378A>C	p.Ile1460Leu	missense_variant	Exon 42 of 50	ENST00000684092.1	NP_001351858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECPAS	ENST00000684092.1	c.4378A>C	p.Ile1460Leu	missense_variant	Exon 42 of 50		NM_001364929.1	ENSP00000507419.1
ECPAS	ENST00000259335.8	c.4912A>C	p.Ile1638Leu	missense_variant	Exon 43 of 51	1		ENSP00000259335.4
ECPAS	ENST00000338205.9	c.4378A>C	p.Ile1460Leu	missense_variant	Exon 41 of 49	5		ENSP00000339889.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248158 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134676

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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: 6.84e-7 AC: 1 AN: 1461162 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726826

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	0.068
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.91	T
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.014	D;D
Sift4G	Benign	0.16	T;T
Vest4		0.47
MutPred		0.51		.;Gain of catalytic residue at I1638 (P = 0.1327);
MVP		0.51
MPC		0.29
ClinPred		0.47	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.39

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

Other links and lift over

dbSNP: rs142217155; hg19: chr9-114134859;