Variant 5-78418852-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004866.6(SCAMP1):c.421A>G(p.Ile141Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,429,388 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SCAMP1
NM_004866.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.10

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SCAMP1	NM_004866.6 linkuse as main transcript	c.421A>G	p.Ile141Val	missense_variant	5/9	ENST00000621999.5
SCAMP1	NM_001290229.2 linkuse as main transcript	c.343A>G	p.Ile115Val	missense_variant	4/8
SCAMP1	XM_011543727.4 linkuse as main transcript	c.421A>G	p.Ile141Val	missense_variant	5/8
SCAMP1	NR_110885.2 linkuse as main transcript	n.476A>G		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAMP1	ENST00000621999.5 linkuse as main transcript	c.421A>G	p.Ile141Val	missense_variant	5/9	1	NM_004866.6	P1	O15126-1
SCAMP1	ENST00000614488.4 linkuse as main transcript	c.421A>G	p.Ile141Val	missense_variant, NMD_transcript_variant	5/8	1			O15126-2
SCAMP1	ENST00000618166.4 linkuse as main transcript	c.343A>G	p.Ile115Val	missense_variant	4/8	2
SCAMP1	ENST00000320280.8 linkuse as main transcript	c.127A>G	p.Ile43Val	missense_variant	2/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1429388

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708440

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.14e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000207

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000831

AC:

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

May 18, 2023

The c.421A>G (p.I141V) alteration is located in exon 5 (coding exon 5) of the SCAMP1 gene. This alteration results from a A to G substitution at nucleotide position 421, causing the isoleucine (I) at amino acid position 141 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

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Benign

0.91

DEOGEN2

Benign

0.065

T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.66

D;D

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Pathogenic

0.82

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.68

MVP

0.80

GERP RS

5.4

Varity_R

0.11

gMVP

0.82

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

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