Variant 12-69800333-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022456.5(RAB3IP):c.1013G>T(p.Ser338Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000898 in 1,559,776 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 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

RAB3IP
NM_022456.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.24

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34237626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3IP	NM_022456.5 linkuse as main transcript	c.1013G>T	p.Ser338Ile	missense_variant	7/11	ENST00000247833.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3IP	ENST00000247833.12 linkuse as main transcript	c.1013G>T	p.Ser338Ile	missense_variant	7/11	1	NM_022456.5	P1	Q96QF0-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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

GnomAD4 exome

AF:

0.00000710

AC:

AN:

1407704

Hom.:

Cov.:

AF XY:

0.00000857

AC XY:

AN XY:

700392

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000830

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

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

Bravo

AF:

0.0000302

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

Nov 21, 2022

The c.1061G>T (p.S354I) alteration is located in exon 7 (coding exon 7) of the RAB3IP gene. This alteration results from a G to T substitution at nucleotide position 1061, causing the serine (S) at amino acid position 354 to be replaced by an isoleucine (I). 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

0.17

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.20

Cadd

Pathogenic

Dann

Uncertain

0.99

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;D;D;.;D;D

M_CAP

Benign

0.061

MetaRNN

Benign

0.34

T;T;T;T;T;T;T

MetaSVM

Benign

-0.49

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.1

D;D;D;D;D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.015

D;D;D;D;D;D;D

Sift4G

Benign

0.062

T;D;T;D;T;T;T

Polyphen

1.0, 1.0

.;D;D;D;.;.;.

Vest4

0.83

MutPred

0.34

.;.;Gain of catalytic residue at S354 (P = 0.025);Gain of catalytic residue at S354 (P = 0.025);.;.;.;

MVP

0.69

MPC

0.53

ClinPred

0.98

GERP RS

5.4

Varity_R

0.66

gMVP

0.59

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