1-155256676-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_005698.4(SCAMP3):​c.895C>G​(p.Arg299Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,158 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. 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. R299W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SCAMP3
NM_005698.4 missense, splice_region

Scores

1
10
7
Splicing: ADA: 0.9848
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.13

Publications

0 publications found
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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCAMP3NM_005698.4 linkc.895C>G p.Arg299Gly missense_variant, splice_region_variant Exon 8 of 9 ENST00000302631.8 NP_005689.2 O14828-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCAMP3ENST00000302631.8 linkc.895C>G p.Arg299Gly missense_variant, splice_region_variant Exon 8 of 9 1 NM_005698.4 ENSP00000307275.3 O14828-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461158
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726920
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39692
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86238
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000360
AC:
4
AN:
1111344
Other (OTH)
AF:
0.00
AC:
0
AN:
60360
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Benign
-0.047
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
34
DANN
Uncertain
1.0
DEOGEN2
Benign
0.083
T;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.89
D
M_CAP
Benign
0.048
D
MetaRNN
Uncertain
0.64
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.7
M;.
PhyloP100
2.1
PrimateAI
Uncertain
0.63
T
PROVEAN
Pathogenic
-4.5
D;D
REVEL
Benign
0.22
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.010
D;D
Polyphen
0.99
D;P
Vest4
0.58
MutPred
0.62
Loss of MoRF binding (P = 0.0214);.;
MVP
0.46
MPC
1.0
ClinPred
0.99
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.54
gMVP
0.79
Mutation Taster
=38/62
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.98
dbscSNV1_RF
Pathogenic
0.84
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs565204943; hg19: chr1-155226467; API