Variant 5-78421854-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004866.6(SCAMP1):c.526G>A(p.Val176Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,730 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 1 hom. )

Consequence

SCAMP1
NM_004866.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90

Variant links:

Genes affected

SCAMP1 (HGNC:10563): (secretory carrier membrane protein 1) 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 these protein family members may function at the same site during vesicular transport rather than in separate pathways. A pseudogene of this gene has been defined on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

SCAMP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32671735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SCAMP1	NM_004866.6 linkuse as main transcript	c.526G>A	p.Val176Ile	missense_variant	6/9	ENST00000621999.5
SCAMP1	NM_001290229.2 linkuse as main transcript	c.448G>A	p.Val150Ile	missense_variant	5/8
SCAMP1	XM_011543727.4 linkuse as main transcript	c.526G>A	p.Val176Ile	missense_variant	6/8
SCAMP1	NR_110885.2 linkuse as main transcript	n.527+2951G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAMP1	ENST00000621999.5 linkuse as main transcript	c.526G>A	p.Val176Ile	missense_variant	6/9	1	NM_004866.6	P1	O15126-1
SCAMP1	ENST00000614488.4 linkuse as main transcript	c.472+2951G>A		intron_variant, NMD_transcript_variant		1			O15126-2
SCAMP1	ENST00000618166.4 linkuse as main transcript	c.448G>A	p.Val150Ile	missense_variant	5/8	2
SCAMP1	ENST00000320280.8 linkuse as main transcript	c.232G>A	p.Val78Ile	missense_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000401

AC:

AN:

249214

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135196

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 SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1461586

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000497

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Aug 09, 2021

The c.526G>A (p.V176I) alteration is located in exon 6 (coding exon 6) of the SCAMP1 gene. This alteration results from a G to A substitution at nucleotide position 526, causing the valine (V) at amino acid position 176 to be replaced by an isoleucine (I). 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

0.096

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Benign

0.83

DEOGEN2

Benign

0.011

T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.071

MetaRNN

Benign

0.33

T;T

MutationAssessor

Uncertain

2.0

M;.

PrimateAI

Uncertain

0.57

Sift4G

Benign

0.50

T;T

Polyphen

0.78

P;.

Vest4

0.58

MVP

0.46

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.59

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