17-5332113-T-G

Position:

• chr17-5332113-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004703.6(RABEP1):​c.328T>G​(p.Trp110Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RABEP1 NM_004703.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.58

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]

RABEP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABEP1	NM_004703.6	c.328T>G	p.Trp110Gly	missense_variant	3/18	ENST00000537505.6	NP_004694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABEP1	ENST00000537505.6	c.328T>G	p.Trp110Gly	missense_variant	3/18	1	NM_004703.6	ENSP00000445408.2
RABEP1	ENST00000341923.10	c.328T>G	p.Trp110Gly	missense_variant	3/17	1		ENSP00000339569.6
RABEP1	ENST00000575475.2	n.364T>G		non_coding_transcript_exon_variant	2/14	1
RABEP1	ENST00000570487.1	c.58T>G	p.Trp20Gly	missense_variant	1/3	2		ENSP00000482983.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Jun 24, 2022

The c.328T>G (p.W110G) alteration is located in exon 3 (coding exon 3) of the RABEP1 gene. This alteration results from a T to G substitution at nucleotide position 328, causing the tryptophan (W) at amino acid position 110 to be replaced by a glycine (G). 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	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	32
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.47	T;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.9	.;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.022	.;D
Sift4G	Benign	0.33	T;T
Polyphen		1.0	D;D
Vest4		0.85
MutPred		0.72		Gain of disorder (P = 0.0132);Gain of disorder (P = 0.0132);
MVP		0.49
ClinPred		0.94	D
GERP RS		6.0
Varity_R		0.53
gMVP		0.56

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: chr17-5235408;