16-28908610-G-T

Position:

• chr16-28908610-G-T

Variant summary

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

The NM_024816.3(RABEP2):​c.1244C>A​(p.Pro415Gln) variant causes a missense, splice region 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. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RABEP2 NM_024816.3 missense, splice_region
• Scores: Splicing: ADA: 0.0006831
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.149

Genes affected

RABEP2 (HGNC:24817): (rabaptin, RAB GTPase binding effector protein 2) Predicted to enable GTPase activator activity and growth factor activity. Involved in regulation of cilium assembly. Located in cytosol; intracellular membrane-bounded organelle; and microtubule organizing center. [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=0.07303837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RABEP2	NM_024816.3	c.1244C>A	p.Pro415Gln	missense_variant, splice_region_variant	8/13	ENST00000358201.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABEP2	ENST00000358201.9	c.1244C>A	p.Pro415Gln	missense_variant, splice_region_variant	8/13	1	NM_024816.3	P1
RABEP2	ENST00000357573.10	c.1148C>A	p.Pro383Gln	missense_variant, splice_region_variant	7/11	1
RABEP2	ENST00000544477.5	c.1031C>A	p.Pro344Gln	missense_variant, splice_region_variant	7/12	2

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

May 06, 2024

The c.1244C>A (p.P415Q) alteration is located in exon 8 (coding exon 8) of the RABEP2 gene. This alteration results from a C to A substitution at nucleotide position 1244, causing the proline (P) at amino acid position 415 to be replaced by a glutamine (Q). 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	0.083
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.2
DANN	Benign	0.62
DEOGEN2	Benign	0.045	.;T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.13	.;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.63	N;N;N
REVEL	Benign	0.017
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.010	B;B;B
Vest4		0.23
MutPred		0.26		.;Gain of helix (P = 0.0425);.;
MVP		0.30
MPC		0.18
ClinPred		0.18	T
GERP RS		-0.70
Varity_R		0.021
gMVP		0.064

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00068
dbscSNV1_RF	Benign	0.19
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: chr16-28919931;