12-69795302-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022456.5(RAB3IP):c.846G>T(p.Gln282His) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB3IP NM_022456.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05

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]

ACMG classification

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=0.20595917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3IP	NM_022456.5	c.846G>T	p.Gln282His	missense_variant	6/11	ENST00000247833.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3IP	ENST00000247833.12	c.846G>T	p.Gln282His	missense_variant	6/11	1	NM_022456.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 01, 2023

The c.894G>T (p.Q298H) alteration is located in exon 6 (coding exon 6) of the RAB3IP gene. This alteration results from a G to T substitution at nucleotide position 894, causing the glutamine (Q) at amino acid position 298 to be replaced by a histidine (H). 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	0.12
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
Cadd	Pathogenic	26
Dann	Uncertain	1.0
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D;D;D;D;D;.;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.42	N;N;N;N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.076	T;D;T;T;T;T;T
Sift4G	Benign	0.39	T;T;T;T;T;T;T
Polyphen		0.99, 0.94, 0.99	.;D;P;D;P;.;.
Vest4		0.45
MutPred		0.23		.;.;.;Gain of phosphorylation at S296 (P = 0.2045);Gain of phosphorylation at S296 (P = 0.2045);.;.;
MVP		0.53
MPC		0.42
ClinPred		0.68	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.098
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-70189082;