Menu
GeneBe

15-74852183-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005697.5(SCAMP2):c.229G>A(p.Val77Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,523,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SCAMP2
NM_005697.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.410
Variant links:
Genes affected
SCAMP2 (HGNC:10564): (secretory carrier membrane protein 2) This gene product belongs to the SCAMP family of proteins which are secretory carrier membrane proteins. They function as carriers to the cell surface in post-golgi recycling pathways. Different family members are highly related products of distinct genes, and are usually expressed together. These findings suggest that the SCAMPs may function at the same site during vesicular transport rather than in separate pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.047329336).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAMP2NM_005697.5 linkuse as main transcriptc.229G>A p.Val77Met missense_variant 4/9 ENST00000268099.13
SCAMP2NM_001320778.2 linkuse as main transcriptc.358G>A p.Val120Met missense_variant 5/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAMP2ENST00000268099.13 linkuse as main transcriptc.229G>A p.Val77Met missense_variant 4/91 NM_005697.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000117
AC:
16
AN:
1371646
Hom.:
0
Cov.:
29
AF XY:
0.0000118
AC XY:
8
AN XY:
679776
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:
0.0000537
Gnomad4 FIN exome
AF:
0.0000208
Gnomad4 NFE exome
AF:
0.00000936
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152350
Hom.:
0
Cov.:
33
AF XY:
0.0000268
AC XY:
2
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

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 GeneticsMar 24, 2023The c.229G>A (p.V77M) alteration is located in exon 4 (coding exon 4) of the SCAMP2 gene. This alteration results from a G to A substitution at nucleotide position 229, causing the valine (V) at amino acid position 77 to be replaced by a methionine (M). 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
0.098
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
Cadd
Benign
16
Dann
Uncertain
0.98
DEOGEN2
Benign
0.011
T;T;.;T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.12
N
LIST_S2
Uncertain
0.89
D;D;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.047
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.83
L;.;.;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.070
N;N;N;N
REVEL
Benign
0.058
Sift
Benign
0.16
T;T;T;T
Sift4G
Benign
0.16
T;T;.;.
Polyphen
0.94
P;.;.;.
Vest4
0.19
MVP
0.40
MPC
0.50
ClinPred
0.13
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.025
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
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: rs142248311; hg19: chr15-75144524; API