2-53797585-C-T

Position:

chr2-53797585-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM2PM5PP5BP4

The NM_015701.5(ERLEC1):c.419C>T(p.Thr140Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,386 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 Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T140S) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ERLEC1
NM_015701.5 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.32

Variant links:

Genes affected

ERLEC1 (HGNC:25222): (endoplasmic reticulum lectin 1) This gene encodes a resident endoplasmic reticulum (ER) protein that functions in N-glycan recognition. This protein is thought to be involved in ER-associated degradation via its interaction with the membrane-associated ubiquitin ligase complex. It also functions as a regulator of multiple cellular stress-response pathways in a manner that promotes metastatic cell survival. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 21. [provided by RefSeq, Aug 2011]

ERLEC1 links:

GPR75-ASB3 (HGNC:):

GPR75-ASB3 links:

ASB3 (HGNC:16013): (ankyrin repeat and SOCS box containing 3) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2011]

ASB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr2-53797585-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 830377.Status of the report is no_assertion_criteria_provided, 0 stars.

PP5

Variant 2-53797585-C-T is Pathogenic according to our data. Variant chr2-53797585-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 830378.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.26774353). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ERLEC1	NM_015701.5 linkuse as main transcript	c.419C>T	p.Thr140Ile	missense_variant	4/14	ENST00000185150.9
GPR75-ASB3	NM_001164165.2 linkuse as main transcript	c.102-32000G>A		intron_variant
ERLEC1	NM_001127397.3 linkuse as main transcript	c.419C>T	p.Thr140Ile	missense_variant	4/13
ERLEC1	NM_001127398.3 linkuse as main transcript	c.419C>T	p.Thr140Ile	missense_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERLEC1	ENST00000185150.9 linkuse as main transcript	c.419C>T	p.Thr140Ile	missense_variant	4/14	1	NM_015701.5	P3	Q96DZ1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249370

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459386

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Mandibular prognathia

Pathogenic:1

Likely pathogenic, no assertion criteria provided

case-control

Dongguan Key Laboratory of Genetics and Infectious Diseases, Dongguan Institute of Pediatrics

Mar 30, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

.;T;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.8

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.083

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.051

T;T;T

Polyphen

0.92, 0.48

.;P;P

Vest4

0.29

MutPred

0.30

Loss of ubiquitination at K143 (P = 0.0396);Loss of ubiquitination at K143 (P = 0.0396);Loss of ubiquitination at K143 (P = 0.0396);

MVP

0.57

MPC

0.64

ClinPred

0.83

GERP RS

4.6

Varity_R

0.25

gMVP

0.49

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