Genetic Variant SCAMP1:p.His114Arg (chr5-78416647-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004866.6(SCAMP1):c.341A>G(p.His114Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000211 in 1,424,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SCAMP1
NM_004866.6 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004866.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCAMP1	NM_004866.6	MANE Select	c.341A>G	p.His114Arg	missense splice_region	Exon 4 of 9	NP_004857.4
SCAMP1	NM_001290229.2		c.263A>G	p.His88Arg	missense splice_region	Exon 3 of 8	NP_001277158.1	A0A087WXB0
SCAMP1	NR_110885.2		n.396A>G		splice_region non_coding_transcript_exon	Exon 4 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCAMP1	ENST00000621999.5	TSL:1 MANE Select	c.341A>G	p.His114Arg	missense splice_region	Exon 4 of 9	ENSP00000481022.1	O15126-1
SCAMP1	ENST00000614488.4	TSL:1	n.341A>G		splice_region non_coding_transcript_exon	Exon 4 of 8	ENSP00000478071.1	O15126-2
SCAMP1	ENST00000878187.1		c.413A>G	p.His138Arg	missense splice_region	Exon 5 of 10	ENSP00000548246.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1424190

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

705452

show subpopulations

African (AFR)

AF:

0.0000311

AC:

AN:

32156

American (AMR)

AF:

0.00

AC:

AN:

39462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25406

East Asian (EAS)

AF:

0.00

AC:

AN:

37940

South Asian (SAS)

AF:

0.00

AC:

AN:

80672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

9.16e-7

AC:

AN:

1092206

Other (OTH)

AF:

0.0000169

AC:

AN:

59092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.00000378

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

0.11

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.023

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.62

M_CAP

Benign

0.010

MetaRNN

Benign

0.15

MutationAssessor

Benign

1.6

PhyloP100

3.6

PrimateAI

Uncertain

0.61

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.11

MVP

0.39

GERP RS

6.0

PromoterAI

-0.081

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.49

Mutation Taster

=62/38

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.27

Position offset: -1

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