5-172914966-C-T

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

1
13

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]
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]

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
ERGIC1NM_001031711.3 linkc.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
ERGIC1ENST00000393784.8 linkc.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.:
21
Cov.:
32
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.:
25
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.:
21
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.:
21
Cov.:
32
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.:
6
Bravo
AF:
0.00683
TwinsUK
AF:
0.00944
AC:
35
ALSPAC
AF:
0.00830
AC:
32
ESP6500AA
AF:
0.00339
AC:
9
ESP6500EA
AF:
0.0139
AC:
64
ExAC
AF:
0.00719
AC:
812
Asia WGS
AF:
0.00144
AC:
5
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
T
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
N
LIST_S2
Benign
0.33
T
MetaRNN
Benign
0.0023
T
MetaSVM
Benign
-1.1
T
PROVEAN
Benign
-0.97
N
REVEL
Benign
0.013
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.38
T
Polyphen
0.0010
B
Vest4
0.057
ClinPred
0.020
T
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.

Other links and lift over

dbSNP: rs62387381; hg19: chr5-172341969; COSMIC: COSV104639909; API