5-78416647-A-G

Position:

• chr5-78416647-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60

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 (HGNC:):

ACMG classification

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	Protein	UniProt
SCAMP1	NM_004866.6	c.341A>G	p.His114Arg	missense_variant, splice_region_variant	4/9	ENST00000621999.5	NP_004857.4
SCAMP1	NM_001290229.2	c.263A>G	p.His88Arg	missense_variant, splice_region_variant	3/8		NP_001277158.1
SCAMP1	XM_011543727.4	c.341A>G	p.His114Arg	missense_variant, splice_region_variant	4/8		XP_011542029.1
SCAMP1	NR_110885.2	n.396A>G		splice_region_variant, non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAMP1	ENST00000621999.5	c.341A>G	p.His114Arg	missense_variant, splice_region_variant	4/9	1	NM_004866.6	ENSP00000481022.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1424190 Hom.: 0 Cov.: 27 AF XY: 0.00000284 AC XY: 2 AN XY: 705452

Gnomad4 AFR exome AF: 0.0000311

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: 9.16e-7

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.341A>G (p.H114R) alteration is located in exon 4 (coding exon 4) of the SCAMP1 gene. This alteration results from a A to G substitution at nucleotide position 341, causing the histidine (H) at amino acid position 114 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.023	T;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T;T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.66	T;T
Polyphen		0.0	B;.
Vest4		0.11
MVP		0.39
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.49

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

LitVar

Other links and lift over

dbSNP: rs1354791577; hg19: chr5-77712471;