9-5754855-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020829.4(RIC1):​c.1617C>T​(p.Ile539Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000908 in 1,564,044 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 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

RIC1
NM_020829.4 synonymous

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00600
Variant links:
Genes affected
RIC1 (HGNC:17686): (RIC1 homolog, RAB6A GEF complex partner 1) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in several processes, including positive regulation of GTPase activity; regulation of extracellular matrix constituent secretion; and retrograde transport, endosome to Golgi. Located in cytosol and membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Apr 2022]
ERMP1 (HGNC:23703): (endoplasmic reticulum metallopeptidase 1) Predicted to enable metal ion binding activity and metalloexopeptidase activity. Involved in cellular response to oxidative stress. Acts upstream of or within endoplasmic reticulum unfolded protein response. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RIC1NM_020829.4 linkc.1617C>T p.Ile539Ile synonymous_variant Exon 15 of 26 ENST00000414202.7 NP_065880.2 Q4ADV7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RIC1ENST00000414202.7 linkc.1617C>T p.Ile539Ile synonymous_variant Exon 15 of 26 5 NM_020829.4 ENSP00000416696.2 Q4ADV7-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
151924
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000242
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:
0.0000946
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000883
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000321
AC:
8
AN:
249020
Hom.:
0
AF XY:
0.0000446
AC XY:
6
AN XY:
134618
show subpopulations
Gnomad AFR exome
AF:
0.000248
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000354
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000885
AC:
125
AN:
1412002
Hom.:
0
Cov.:
29
AF XY:
0.0000900
AC XY:
63
AN XY:
699876
show subpopulations
Gnomad4 AFR exome
AF:
0.000394
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000131
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000963
Gnomad4 OTH exome
AF:
0.000121
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152042
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000946
Gnomad4 NFE
AF:
0.0000883
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000285
Hom.:
0
Bravo
AF:
0.000174

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Catifa syndrome Uncertain:1
Mar 10, 2023
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.29
CADD
Benign
17
DANN
Benign
0.76
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.35
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.35
Position offset: 8

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: rs573748502; hg19: chr9-5754855; COSMIC: COSV99317934; API