chr17-5346805-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004703.6(RABEP1):c.664C>A(p.His222Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000318 in 1,572,212 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
RABEP1
NM_004703.6 missense
NM_004703.6 missense
Scores
2
5
10
Clinical Significance
Conservation
PhyloP100: 7.49
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]
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ACMG classification
Classification made for transcript
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RABEP1 | NM_004703.6 | c.664C>A | p.His222Asn | missense_variant | 6/18 | ENST00000537505.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RABEP1 | ENST00000537505.6 | c.664C>A | p.His222Asn | missense_variant | 6/18 | 1 | NM_004703.6 | P1 | |
RABEP1 | ENST00000341923.10 | c.664C>A | p.His222Asn | missense_variant | 6/17 | 1 | |||
RABEP1 | ENST00000575475.2 | n.700C>A | non_coding_transcript_exon_variant | 5/14 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000128 AC: 3AN: 234614Hom.: 0 AF XY: 0.0000157 AC XY: 2AN XY: 127410
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GnomAD4 exome AF: 0.00000282 AC: 4AN: 1420094Hom.: 0 Cov.: 30 AF XY: 0.00000284 AC XY: 2AN XY: 704844
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74298
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 29, 2023 | The c.664C>A (p.H222N) alteration is located in exon 6 (coding exon 6) of the RABEP1 gene. This alteration results from a C to A substitution at nucleotide position 664, causing the histidine (H) at amino acid position 222 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
REVEL
Benign
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Gain of catalytic residue at H222 (P = 0.1177);Gain of catalytic residue at H222 (P = 0.1177);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at