2-53796012-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_015701.5(ERLEC1):c.347G>C(p.Arg116Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,587,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ERLEC1
NM_015701.5 missense, splice_region

Scores

Splicing: ADA: 0.9935

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.86

Publications

1 publications found

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:40043): (GPR75-ASB3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring GPR75 (G protein-coupled receptor 75) and ASB3 (ankyrin repeat and SOCS box containing 3) on chromosome 2. The transcript includes exons from both GPR75 and ASB3 and translation initiates in the 5' non-coding exon of GPR75. The resulting protein has a novel N-terminus but is otherwise identical to that encoded by ASB3.[provided by RefSeq, Feb 2011]

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015701.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERLEC1	NM_015701.5	MANE Select	c.347G>C	p.Arg116Thr	missense splice_region	Exon 3 of 14	NP_056516.2
ERLEC1	NM_001127397.3		c.347G>C	p.Arg116Thr	missense splice_region	Exon 3 of 13	NP_001120869.1	Q96DZ1-3
ERLEC1	NM_001127398.3		c.347G>C	p.Arg116Thr	missense splice_region	Exon 3 of 13	NP_001120870.1	Q96DZ1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERLEC1	ENST00000185150.9	TSL:1 MANE Select	c.347G>C	p.Arg116Thr	missense splice_region	Exon 3 of 14	ENSP00000185150.4	Q96DZ1-1
ERLEC1	ENST00000378239.5	TSL:1	c.347G>C	p.Arg116Thr	missense splice_region	Exon 3 of 13	ENSP00000367485.5	Q96DZ1-2
ERLEC1	ENST00000952242.1		c.347G>C	p.Arg116Thr	missense splice_region	Exon 3 of 14	ENSP00000622301.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000860

AC:

AN:

232480

AF XY:

0.00000792

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1435430

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

714574

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31964

American (AMR)

AF:

0.00

AC:

AN:

39450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25480

East Asian (EAS)

AF:

0.00

AC:

AN:

38990

South Asian (SAS)

AF:

0.00

AC:

AN:

82288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000164

AC:

AN:

1099368

Other (OTH)

AF:

0.0000505

AC:

AN:

59362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Pathogenic

1.2

Eigen_PC

Pathogenic

1.1

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.057

MetaRNN

Pathogenic

0.87

MetaSVM

Benign

-0.70

MutationAssessor

Pathogenic

3.3

PhyloP100

9.9

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.60

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.92

MutPred

0.61

Gain of phosphorylation at R116 (P = 0.069)

MVP

0.89

MPC

0.99

ClinPred

0.98

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.70

gMVP

0.84

Mutation Taster

=33/67

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.92

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over