Variant 15-74854064-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005697.5(SCAMP2):c.182C>T(p.Ala61Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000952 in 1,614,032 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00099 ( 1 hom. )

Consequence

SCAMP2
NM_005697.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.44

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.104956746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAMP2	NM_005697.5 linkuse as main transcript	c.182C>T	p.Ala61Val	missense_variant	3/9	ENST00000268099.13	NP_005688.2	O15127A0A140VK92
SCAMP2	NM_001320778.2 linkuse as main transcript	c.182C>T	p.Ala61Val	missense_variant	3/10		NP_001307707.1	A8K769

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAMP2	ENST00000268099.13 linkuse as main transcript	c.182C>T	p.Ala61Val	missense_variant	3/9	1	NM_005697.5	ENSP00000268099.9		O15127

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000612

AC:

154

AN:

251436

Hom.:

AF XY:

0.000640

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.000941

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000993

AC:

1451

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000986

AC XY:

717

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000565

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000943

Hom.:

Bravo

AF:

0.000480

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000610

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.00107

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

Jul 13, 2021

The c.182C>T (p.A61V) alteration is located in exon 3 (coding exon 3) of the SCAMP2 gene. This alteration results from a C to T substitution at nucleotide position 182, causing the alanine (A) at amino acid position 61 to be replaced by a valine (V). 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

0.33

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;T;.;T

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

M;.;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.0090

D;D;.;.

Polyphen

1.0

D;.;.;.

Vest4

0.62

MVP

0.72

MPC

0.87

ClinPred

0.096

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over