12-69813026-G-C

Variant summary

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

The NM_022456.5(RAB3IP):c.1293G>C(p.Gln431His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.67

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3IP	NM_022456.5	c.1293G>C	p.Gln431His	missense_variant	10/11	ENST00000247833.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3IP	ENST00000247833.12	c.1293G>C	p.Gln431His	missense_variant	10/11	1	NM_022456.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Mar 29, 2022

The c.1341G>C (p.Q447H) alteration is located in exon 10 (coding exon 10) of the RAB3IP gene. This alteration results from a G to C substitution at nucleotide position 1341, causing the glutamine (Q) at amino acid position 447 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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;.;D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.55	D;D;D;D;D
MetaSVM	Benign	-0.77	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.57	N;N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.073	T;T;D;D;D
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		1.0	.;D;.;.;.
Vest4		0.78
MutPred		0.14		.;Gain of helix (P = 0.062);.;.;.;
MVP		0.67
MPC		0.50
ClinPred		0.90	D
GERP RS		4.2
Varity_R		0.29
gMVP		0.66

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: chr12-70206806;