Variant 12-1083521-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_178040.4(ERC1):c.1027G>A(p.Val343Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,320 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ERC1
NM_178040.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

ERC1 (HGNC:17072): (ELKS/RAB6-interacting/CAST family member 1) The protein encoded by this gene is a member of a family of RIM-binding proteins. RIMs are active zone proteins that regulate neurotransmitter release. This gene has been found fused to the receptor-type tyrosine kinase gene RET by gene rearrangement due to the translocation t(10;12)(q11;p13) in thyroid papillary carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ERC1 links:

ERC1 (HGNC:):

ERC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10701224).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERC1	NM_178040.4 linkuse as main transcript	c.1027G>A	p.Val343Ile	missense_variant	3/19	ENST00000360905.9	NP_829884.1	Q8IUD2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERC1	ENST00000360905.9 linkuse as main transcript	c.1027G>A	p.Val343Ile	missense_variant	3/19	1	NM_178040.4	ENSP00000354158.3		Q8IUD2-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152176

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

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461144

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.1027G>A (p.V343I) alteration is located in exon 1 (coding exon 1) of the ERC1 gene. This alteration results from a G to A substitution at nucleotide position 1027, causing the valine (V) at amino acid position 343 to be replaced by an isoleucine (I). 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

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.084

.;.;.;T;.;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

0.044

FATHMM_MKL

Uncertain

0.77

M_CAP

Benign

0.0068

MetaRNN

Benign

0.11

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.16

N;.;.;N;N;N;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.24

N;N;.;N;N;.;N

REVEL

Benign

0.066

Sift

Benign

0.41

T;T;.;T;T;.;T

Sift4G

Benign

0.67

T;T;T;T;T;T;T

Polyphen

0.030

B;.;.;B;B;B;.

Vest4

0.22

MutPred

0.37

Gain of catalytic residue at L346 (P = 0.0129);Gain of catalytic residue at L346 (P = 0.0129);.;Gain of catalytic residue at L346 (P = 0.0129);Gain of catalytic residue at L346 (P = 0.0129);Gain of catalytic residue at L346 (P = 0.0129);Gain of catalytic residue at L346 (P = 0.0129);

MVP

0.29

MPC

0.30

ClinPred

0.34

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.065

gMVP

0.19

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