17-5308697-C-A

Variant names:

• chr17-5308697-C-A
• rs372045538
• NM_004703.6:c.38C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004703.6(RABEP1):​c.38C>A​(p.Ser13Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S13C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RABEP1 NM_004703.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• Publications: 0 publications found

Genes affected

RABEP1 (HGNC:17677): (rabaptin, RAB GTPase binding effector protein 1) Enables protein domain specific binding activity and protein homodimerization activity. Involved in vesicle-mediated transport. Located in endocytic vesicle and endosome. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2526336).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004703.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABEP1	NM_004703.6	MANE Select	c.38C>A	p.Ser13Tyr	missense	Exon 2 of 18	NP_004694.2
	RABEP1	NM_001083585.3		c.38C>A	p.Ser13Tyr	missense	Exon 2 of 17	NP_001077054.1	Q15276-2
	RABEP1	NM_001291582.2		c.38C>A	p.Ser13Tyr	missense	Exon 2 of 5	NP_001278511.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABEP1	ENST00000537505.6	TSL:1 MANE Select	c.38C>A	p.Ser13Tyr	missense	Exon 2 of 18	ENSP00000445408.2	Q15276-1
	RABEP1	ENST00000341923.10	TSL:1	c.38C>A	p.Ser13Tyr	missense	Exon 2 of 17	ENSP00000339569.6	Q15276-2
	RABEP1	ENST00000575475.2	TSL:1	n.200-23252C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.7
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.069
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.55	P
Vest4		0.35
MutPred		0.26		Gain of phosphorylation at S13 (P = 0.0524)
MVP		0.24
ClinPred		0.77	D
GERP RS		5.6
Varity_R		0.28
gMVP		0.32

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

Other links and lift over

dbSNP: rs372045538; hg19: chr17-5211992;