NM_024816.3:c.1589G>T

Variant names:

• chr16-28905416-C-A
• rs769823303
• NM_024816.3:c.1589G>T

Variant summary

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

The NM_024816.3(RABEP2):​c.1589G>T​(p.Arg530Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RABEP2 NM_024816.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP2	NM_024816.3	c.1589G>T	p.Arg530Leu	missense_variant	Exon 12 of 13	ENST00000358201.9	NP_079092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP2	ENST00000358201.9	c.1589G>T	p.Arg530Leu	missense_variant	Exon 12 of 13	1	NM_024816.3	ENSP00000350934.4
RABEP2	ENST00000357573.10	c.1481G>T	p.Arg494Leu	missense_variant	Exon 10 of 11	1		ENSP00000350186.6
RABEP2	ENST00000544477.5	c.1376G>T	p.Arg459Leu	missense_variant	Exon 11 of 12	2		ENSP00000442798.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453960 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 722544

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000229

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.0096	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	.;D;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.3	.;M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D;D;D
Sift4G	Benign	0.16	T;D;T
Polyphen		0.99	D;P;D
Vest4		0.61
MutPred		0.37		.;Loss of MoRF binding (P = 0.0047);.;
MVP		0.66
MPC		0.29
ClinPred		0.97	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 20

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs769823303; hg19: chr16-28916737;