Variant 9-5629335-A-C 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.26A>C(p.Lys9Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000673 in 1,530,070 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 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

RIC1
NM_020829.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

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:

ENSG00000286162 (HGNC:):

ENSG00000286162 links:

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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=0.2587878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIC1	NM_020829.4 link	c.26A>C	p.Lys9Thr	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 link	c.26A>C	p.Lys9Thr	missense_variant	1/26	5	NM_020829.4	ENSP00000416696.2	Q4ADV7-1
RIC1	ENST00000251879.10 link	c.26A>C	p.Lys9Thr	missense_variant	1/22	1		ENSP00000251879.6	Q4ADV7-2
RIC1	ENST00000418622.7 link	c.26A>C	p.Lys9Thr	missense_variant	1/25	5		ENSP00000402240.4	Q4ADV7-3
ENSG00000286162	ENST00000661858.1 link	n.182+232T>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000547

AC:

AN:

127980

Hom.:

AF XY:

0.0000286

AC XY:

AN XY:

69864

show subpopulations

Gnomad AFR exome

AF:

0.000908

Gnomad AMR exome

AF:

0.0000869

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000290

AC:

AN:

1377842

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

679860

show subpopulations

Gnomad4 AFR exome

AF:

0.00107

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000256

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000693

GnomAD4 genome

AF:

0.000414

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000480

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

Jun 25, 2024

The c.26A>C (p.K9T) alteration is located in exon 1 (coding exon 1) of the RIC1 gene. This alteration results from a A to C substitution at nucleotide position 26, causing the lysine (K) at amino acid position 9 to be replaced by a threonine (T). 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

Pathogenic

0.76

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;.;T

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.97

L;L;L

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.2

D;.;D

REVEL

Benign

0.22

Sift

Uncertain

0.0030

D;.;D

Sift4G

Uncertain

0.010

D;D;D

Vest4

0.41

MutPred

0.49

Loss of methylation at K9 (P = 0.004);Loss of methylation at K9 (P = 0.004);Loss of methylation at K9 (P = 0.004);

MVP

0.043

ClinPred

0.20

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.63

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