17-5282508-T-C

Variant names:

• chr17-5282508-T-C
• NM_004703.6:c.22T>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004703.6(RABEP1):​c.22T>C​(p.Ser8Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000271 in 1,106,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RABEP1 NM_004703.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.217

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053823113).
• BP6: Variant 17-5282508-T-C is Benign according to our data. Variant chr17-5282508-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2534515.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP1	NM_004703.6	c.22T>C	p.Ser8Pro	missense_variant	Exon 1 of 18	ENST00000537505.6	NP_004694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP1	ENST00000537505.6	c.22T>C	p.Ser8Pro	missense_variant	Exon 1 of 18	1	NM_004703.6	ENSP00000445408.2
RABEP1	ENST00000341923.10	c.22T>C	p.Ser8Pro	missense_variant	Exon 1 of 17	1		ENSP00000339569.6
RABEP1	ENST00000575475.2	n.187T>C		non_coding_transcript_exon_variant	Exon 1 of 14	1
RABEP1	ENST00000575991.1	c.22T>C	p.Ser8Pro	missense_variant	Exon 1 of 3	4		ENSP00000459550.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000271 AC: 3 AN: 1106078 Hom.: 0 Cov.: 30 AF XY: 0.00000189 AC XY: 1 AN XY: 530224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000214

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 07, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.0062	T;T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.18	T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.054	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	.;N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.28	.;N;N
REVEL	Benign	0.086
Sift	Benign	0.28	.;T;T
Sift4G	Benign	0.34	.;T;T
Polyphen		0.0	.;B;B
Vest4		0.072, 0.075
MutPred		0.13		Loss of phosphorylation at S8 (P = 0.0217);Loss of phosphorylation at S8 (P = 0.0217);Loss of phosphorylation at S8 (P = 0.0217);
MVP		0.18
ClinPred		0.096	T
GERP RS		-0.053
Varity_R		0.11
gMVP		0.12

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: chr17-5185803;