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GeneBe

1-155256676-G-A

Variant summary

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

The NM_005698.4(SCAMP3):c.895C>T(p.Arg299Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,461,158 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/2 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R299Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SCAMP3
NM_005698.4 missense, splice_region

Scores

2
9
7
Splicing: ADA: 0.9996
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13
Variant links:
Genes affected
SCAMP3 (HGNC:10565): (secretory carrier membrane protein 3) This gene encodes an integral membrane protein that belongs to the secretory carrier membrane protein family. The encoded protein functions as a carrier to the cell surface in post-golgi recycling pathways. This protein is also involved in protein trafficking in endosomal pathways. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]

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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
SCAMP3NM_005698.4 linkuse as main transcriptc.895C>T p.Arg299Trp missense_variant, splice_region_variant 8/9 ENST00000302631.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAMP3ENST00000302631.8 linkuse as main transcriptc.895C>T p.Arg299Trp missense_variant, splice_region_variant 8/91 NM_005698.4 P1O14828-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251452
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1461158
Hom.:
0
Cov.:
30
AF XY:
0.00000825
AC XY:
6
AN XY:
726920
show subpopulations
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsDec 15, 2022The c.895C>T (p.R299W) alteration is located in exon 8 (coding exon 8) of the SCAMP3 gene. This alteration results from a C to T substitution at nucleotide position 895, causing the arginine (R) at amino acid position 299 to be replaced by a tryptophan (W). 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
Benign
0.31
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.30
Cadd
Pathogenic
35
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.095
T;.
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.81
D
M_CAP
Benign
0.059
D
MetaRNN
Uncertain
0.58
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.7
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-5.0
D;D
REVEL
Uncertain
0.29
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;D
Vest4
0.57
MutPred
0.64
Gain of ubiquitination at K298 (P = 0.0428);.;
MVP
0.57
MPC
0.96
ClinPred
0.96
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.53
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.89
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs565204943; hg19: chr1-155226467; API