Variant 9-5629399-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020829.4(RIC1):c.90G>T(p.Gln30His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000506 in 1,382,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RIC1
NM_020829.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12

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]

RIC1 links:

RIC1 (HGNC:):

RIC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12982884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIC1	NM_020829.4 linkuse as main transcript	c.90G>T	p.Gln30His	missense_variant	1/26	ENST00000414202.7	NP_065880.2	Q4ADV7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RIC1	ENST00000414202.7 linkuse as main transcript	c.90G>T	p.Gln30His	missense_variant	1/26	5	NM_020829.4	ENSP00000416696.2	Q4ADV7-1
RIC1	ENST00000251879.10 linkuse as main transcript	c.90G>T	p.Gln30His	missense_variant	1/22	1		ENSP00000251879.6	Q4ADV7-2
RIC1	ENST00000418622.7 linkuse as main transcript	c.90G>T	p.Gln30His	missense_variant	1/25	5		ENSP00000402240.4	Q4ADV7-3
ENSG00000286162	ENST00000661858.1 linkuse as main transcript	n.182+168C>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151926

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000506

AC:

AN:

1382150

Hom.:

Cov.:

AF XY:

0.00000880

AC XY:

AN XY:

682102

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000658

AC:

AN:

151926

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Oct 25, 2024

The c.90G>T (p.Q30H) alteration is located in exon 1 (coding exon 1) of the RIC1 gene. This alteration results from a G to T substitution at nucleotide position 90, causing the glutamine (Q) at amino acid position 30 to be replaced by a histidine (H). 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

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.038

.;.;T

Eigen

Benign

-0.089

Eigen_PC

Benign

-0.079

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.66

T;T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;L

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.84

N;.;N

REVEL

Benign

0.010

Sift

Benign

0.24

T;.;T

Sift4G

Benign

0.15

T;T;T

Vest4

0.10

MutPred

0.21

Gain of disorder (P = 0.1384);Gain of disorder (P = 0.1384);Gain of disorder (P = 0.1384);

MVP

0.043

ClinPred

0.20

GERP RS

1.8

Varity_R

0.12

gMVP

0.52

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