11-61906519-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013401.4(RAB3IL1):​c.604G>A​(p.Ala202Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 1,555,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A202S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

RAB3IL1
NM_013401.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.944
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.037370384).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB3IL1NM_013401.4 linkc.604G>A p.Ala202Thr missense_variant Exon 5 of 10 ENST00000394836.7 NP_037533.2 Q8TBN0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB3IL1ENST00000394836.7 linkc.604G>A p.Ala202Thr missense_variant Exon 5 of 10 1 NM_013401.4 ENSP00000378313.2 Q8TBN0-1
RAB3IL1ENST00000301773.9 linkc.579+874G>A intron_variant Intron 4 of 8 1 ENSP00000301773.5 Q8TBN0-2
RAB3IL1ENST00000531922.2 linkc.745G>A p.Ala249Thr missense_variant Exon 5 of 11 3 ENSP00000435444.2 E9PK89

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152002
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000424
AC:
7
AN:
164926
Hom.:
0
AF XY:
0.0000569
AC XY:
5
AN XY:
87842
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.000105
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000620
AC:
87
AN:
1403812
Hom.:
0
Cov.:
31
AF XY:
0.0000721
AC XY:
50
AN XY:
693450
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000544
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000738
Gnomad4 OTH exome
AF:
0.0000859
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152002
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74236
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000122
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000425
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 22, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.604G>A (p.A202T) alteration is located in exon 5 (coding exon 5) of the RAB3IL1 gene. This alteration results from a G to A substitution at nucleotide position 604, causing the alanine (A) at amino acid position 202 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
Benign
0.064
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
8.7
DANN
Benign
0.94
DEOGEN2
Benign
0.011
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.65
T;.
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.037
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.67
N;.
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.56
N;N
REVEL
Benign
0.041
Sift
Benign
0.26
T;T
Sift4G
Benign
0.59
T;.
Polyphen
0.0040
B;.
Vest4
0.095
MVP
0.19
MPC
0.082
ClinPred
0.024
T
GERP RS
0.82
Varity_R
0.031
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs774752186; hg19: chr11-61673991; API