Variant 12-69755521-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022456.5(RAB3IP):c.113G>A(p.Ser38Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

RAB3IP
NM_022456.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

Variant links:

Genes affected

RAB3IP (HGNC:16508): (RAB3A interacting protein) Enables guanyl-nucleotide exchange factor activity and identical protein binding activity. Involved in cilium assembly; protein localization to organelle; and protein targeting to membrane. Located in centrosome; cytosol; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RAB3IP links:

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=0.015305847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3IP	NM_022456.5 linkuse as main transcript	c.113G>A	p.Ser38Asn	missense_variant	2/11	ENST00000247833.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3IP	ENST00000247833.12 linkuse as main transcript	c.113G>A	p.Ser38Asn	missense_variant	2/11	1	NM_022456.5	P1	Q96QF0-2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

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:

0.000107

AC:

AN:

251478

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00147

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:

0.0000308

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000882

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jan 03, 2024

The c.161G>A (p.S54N) alteration is located in exon 2 (coding exon 2) of the RAB3IP gene. This alteration results from a G to A substitution at nucleotide position 161, causing the serine (S) at amino acid position 54 to be replaced by an asparagine (N). 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

0.093

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.61

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.043

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.74

T;T;T;T;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.015

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.97

D;D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.44

N;N;N;N;N;N

REVEL

Benign

0.088

Sift

Benign

0.23

T;T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T;T

Polyphen

0.0030, 0.0, 0.0010

.;B;B;.;B;B

Vest4

0.095

MVP

0.56

MPC

0.092

ClinPred

0.077

GERP RS

5.7

Varity_R

0.059

gMVP

0.32

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

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