5-172935197-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001031711.3(ERGIC1):c.652G>A(p.Ala218Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,613,936 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 14 hom. )

Consequence

ERGIC1
NM_001031711.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

ERGIC1 (HGNC:29205): (endoplasmic reticulum-golgi intermediate compartment 1) This gene encodes a cycling membrane protein which is an endoplasmic reticulum-golgi intermediate compartment (ERGIC) protein which interacts with other members of this protein family to increase their turnover. [provided by RefSeq, Jul 2008]

ERGIC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015652359).

BP6

Variant 5-172935197-G-A is Benign according to our data. Variant chr5-172935197-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ERGIC1	NM_001031711.3 linkuse as main transcript	c.652G>A	p.Ala218Thr	missense_variant	9/10	ENST00000393784.8
ERGIC1	XM_011534597.2 linkuse as main transcript	c.724G>A	p.Ala242Thr	missense_variant	9/10
ERGIC1	XM_047417411.1 linkuse as main transcript	c.376G>A	p.Ala126Thr	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERGIC1	ENST00000393784.8 linkuse as main transcript	c.652G>A	p.Ala218Thr	missense_variant	9/10	1	NM_001031711.3	P1	Q969X5-1

Frequencies

GnomAD3 genomes

AF:

0.00218

AC:

332

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00298

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00220

AC:

554

AN:

251444

Hom.:

AF XY:

0.00208

AC XY:

282

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00605

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.00213

Gnomad NFE exome

AF:

0.00315

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00251

AC:

3665

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

1771

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00670

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000893

Gnomad4 FIN exome

AF:

0.00210

Gnomad4 NFE exome

AF:

0.00276

Gnomad4 OTH exome

AF:

0.00230

GnomAD4 genome

AF:

0.00218

AC:

331

AN:

152086

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000579

Gnomad4 AMR

AF:

0.00295

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00299

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00297

Hom.:

Bravo

AF:

0.00221

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00210

AC:

255

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00322

EpiControl

AF:

0.00332

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

ERGIC1: BP4, BS2 -

ERGIC1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 06, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.11

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.031

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0054

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.46

REVEL

Benign

0.18

Sift

Benign

0.87

Sift4G

Benign

0.36

Polyphen

0.084

Vest4

0.82

MVP

0.29

MPC

0.66

ClinPred

0.067

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

gMVP

0.77

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