Variant 15-74854038-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005697.5(SCAMP2):c.208A>T(p.Thr70Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,614,058 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 33 hom. )

Consequence

SCAMP2
NM_005697.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0350

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038162172).

BP6

Variant 15-74854038-T-A is Benign according to our data. Variant chr15-74854038-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645551.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAMP2	NM_005697.5 linkuse as main transcript	c.208A>T	p.Thr70Ser	missense_variant	3/9	ENST00000268099.13	NP_005688.2	O15127A0A140VK92
SCAMP2	NM_001320778.2 linkuse as main transcript	c.208A>T	p.Thr70Ser	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.208A>T	p.Thr70Ser	missense_variant	3/9	1	NM_005697.5	ENSP00000268099.9		O15127

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

527

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00589

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00316

AC:

795

AN:

251384

Hom.:

AF XY:

0.00322

AC XY:

437

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.00570

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00605

AC:

8837

AN:

1461736

Hom.:

Cov.:

AF XY:

0.00585

AC XY:

4252

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00246

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.00737

Gnomad4 OTH exome

AF:

0.00679

GnomAD4 genome

AF:

0.00346

AC:

527

AN:

152322

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

240

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00590

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00548

Hom.:

Bravo

AF:

0.00379

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00733

AC:

ExAC

AF:

0.00308

AC:

374

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00583

EpiControl

AF:

0.00688

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SCAMP2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.0

DANN

Benign

0.83

DEOGEN2

Benign

0.0083

T;T;.;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.59

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.52

T;T;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.0038

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.46

N;.;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.46

N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.43

T;T;T;T

Sift4G

Benign

0.67

T;T;.;.

Polyphen

0.018

B;.;.;.

Vest4

0.25

MutPred

0.23

Loss of glycosylation at T70 (P = 0.0863);.;.;Loss of glycosylation at T70 (P = 0.0863);

MVP

0.30

MPC

0.33

ClinPred

0.0015

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.030

gMVP

0.19

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