dbSNP rs774752186: RAB3IL1:p.Ala202Ser (chr11-61906519-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013401.4(RAB3IL1):c.604G>T(p.Ala202Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A202D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAB3IL1
NM_013401.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.944

Publications

0 publications found

Variant links:

Genes affected

RAB3IL1 (HGNC:9780): (RAB3A interacting protein like 1) This gene encodes a guanine nucleotide exchange factor for the ras-related protein Rab3A. The encoded protein binds Rab3a and the inositol hexakisphosphate kinase InsP6K1. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 7. [provided by RefSeq, Nov 2012]

RAB3IL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04574004).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013401.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3IL1	NM_013401.4	MANE Select	c.604G>T	p.Ala202Ser	missense	Exon 5 of 10	NP_037533.2
	RAB3IL1	NM_001271686.2		c.579+874G>T		intron	N/A	NP_001258615.1	Q8TBN0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB3IL1	ENST00000394836.7	TSL:1 MANE Select	c.604G>T	p.Ala202Ser	missense	Exon 5 of 10	ENSP00000378313.2	Q8TBN0-1
RAB3IL1	ENST00000301773.9	TSL:1	c.579+874G>T		intron	N/A	ENSP00000301773.5	Q8TBN0-2
RAB3IL1	ENST00000531922.2	TSL:3	c.745G>T	p.Ala249Ser	missense	Exon 5 of 11	ENSP00000435444.2	E9PK89

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1403810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693448

African (AFR)

AF:

0.00

AC:

AN:

32168

American (AMR)

AF:

0.00

AC:

AN:

36452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25156

East Asian (EAS)

AF:

0.00

AC:

AN:

36786

South Asian (SAS)

AF:

0.00

AC:

AN:

80036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4360

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083586

Other (OTH)

AF:

0.00

AC:

AN:

58208

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.9

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0083

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.76

M_CAP

Benign

0.014

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.94

PrimateAI

Benign

0.24

PROVEAN

Benign

0.17

REVEL

Benign

0.050

Sift

Benign

0.61

Sift4G

Benign

0.89

Polyphen

0.010

Vest4

0.12

MutPred

0.21

Gain of glycosylation at A202 (P = 0.0276)

MVP

0.41

MPC

0.080

ClinPred

0.031

GERP RS

0.82

Varity_R

0.034

gMVP

0.17

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over