Genetic Variant SCAMP2:p.Ala35Glu (chr15-74854603-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005697.5(SCAMP2):c.104C>A(p.Ala35Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000213 in 1,454,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. A35V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SCAMP2
NM_005697.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.36

Publications

2 publications found

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]

SCAMP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04825321).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005697.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAMP2	NM_005697.5	MANE Select	c.104C>A	p.Ala35Glu	missense	Exon 2 of 9	NP_005688.2
	SCAMP2	NM_001320778.2		c.104C>A	p.Ala35Glu	missense	Exon 2 of 10	NP_001307707.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCAMP2	ENST00000268099.13	TSL:1 MANE Select	c.104C>A	p.Ala35Glu	missense	Exon 2 of 9	ENSP00000268099.9	O15127
SCAMP2	ENST00000894365.1		c.104C>A	p.Ala35Glu	missense	Exon 2 of 10	ENSP00000564424.1
SCAMP2	ENST00000960462.1		c.104C>A	p.Ala35Glu	missense	Exon 2 of 9	ENSP00000630521.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000170

AC:

AN:

235420

AF XY:

0.0000235

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000378

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1454328

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

722692

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33310

American (AMR)

AF:

0.00

AC:

AN:

43884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25864

East Asian (EAS)

AF:

0.00

AC:

AN:

39388

South Asian (SAS)

AF:

0.00

AC:

AN:

84598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000271

AC:

AN:

1108620

Other (OTH)

AF:

0.0000167

AC:

AN:

60012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0051

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.036

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.83

M_CAP

Benign

0.0023

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

PhyloP100

5.4

PrimateAI

Uncertain

0.50

PROVEAN

Benign

2.8

REVEL

Benign

0.093

Sift

Benign

0.77

Sift4G

Benign

0.95

Polyphen

0.0

Vest4

0.29

MutPred

0.24

Gain of solvent accessibility (P = 0.0789)

MVP

0.27

MPC

0.43

ClinPred

0.32

GERP RS

4.8

PromoterAI

0.0087

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.084

gMVP

0.16

Mutation Taster

=58/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over