Genetic Variant ERGIC1:p.Ser168Leu (chr5-172914966-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000326654.7(ERGIC1):c.503C>T(p.Ser168Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,445,584 control chromosomes in the GnomAD database, including 180 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 21 hom., cov: 32)

Exomes 𝑓: 0.012 ( 159 hom. )

Consequence

ERGIC1
ENST00000326654.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.866

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:

MIR10523 (HGNC:54013): (microRNA 10523) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR10523 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022776425).

BP6

Variant 5-172914966-C-T is Benign according to our data. Variant chr5-172914966-C-T is described in ClinVar as [Benign]. Clinvar id is 2656079.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERGIC1	NM_001031711.3 link	c.375+128C>T		intron_variant	Intron 5 of 9	ENST00000393784.8	NP_001026881.1	Q969X5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERGIC1	ENST00000393784.8 link	c.375+128C>T		intron_variant	Intron 5 of 9	1	NM_001031711.3	ENSP00000377374.3		Q969X5-1

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1634

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0550

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.0110

AC:

1794

AN:

163724

Hom.:

AF XY:

0.0101

AC XY:

874

AN XY:

86692

show subpopulations

Gnomad AFR exome

AF:

0.00226

Gnomad AMR exome

AF:

0.00221

Gnomad ASJ exome

AF:

0.00105

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00182

Gnomad FIN exome

AF:

0.0482

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.00931

GnomAD4 exome

AF:

0.0116

AC:

15001

AN:

1293320

Hom.:

159

Cov.:

AF XY:

0.0113

AC XY:

7253

AN XY:

643904

show subpopulations

Gnomad4 AFR exome

AF:

0.00142

Gnomad4 AMR exome

AF:

0.00267

Gnomad4 ASJ exome

AF:

0.000978

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00165

Gnomad4 FIN exome

AF:

0.0459

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.00966

GnomAD4 genome

AF:

0.0107

AC:

1634

AN:

152264

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

930

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00221

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0550

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00683

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00339

AC:

ESP6500EA

AF:

0.0139

AC:

ExAC

AF:

0.00719

AC:

812

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ERGIC1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.0070

DANN

Benign

0.14

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.97

REVEL

Benign

0.013

Sift

Pathogenic

0.0

Sift4G

Benign

0.38

Polyphen

0.0010

Vest4

0.057

ClinPred

0.020

GERP RS

-5.0

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