rs3765066

Variant names:

• chr15-74848513-G-A
• rs3765066
• NM_005697.5:c.734+87C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005697.5(SCAMP2):​c.734+87C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 829,814 control chromosomes in the GnomAD database, including 146,808 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (21074 hom., cov: 31)
  • Exomes 𝑓: 0.59 (125734 hom.)
• Consequence: SCAMP2 NM_005697.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 27 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005697.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAMP2	NM_005697.5	MANE Select	c.734+87C>T		intron	N/A	NP_005688.2
	SCAMP2	NM_001320778.2		c.863+87C>T		intron	N/A	NP_001307707.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAMP2	ENST00000268099.13	TSL:1 MANE Select	c.734+87C>T		intron	N/A	ENSP00000268099.9
	SCAMP2	ENST00000567638.1	TSL:2	n.591C>T		non_coding_transcript_exon	Exon 4 of 4
	SCAMP2	ENST00000566480.5	TSL:5	c.614+87C>T		intron	N/A	ENSP00000455377.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73594 AN: 151886 Hom.: 21079 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.595 AC: 402977 AN: 677810 Hom.: 125734 Cov.: 9 AF XY: 0.583 AC XY: 206237 AN XY: 353888

African (AFR) AF: 0.168 AC: 2817 AN: 16744

American (AMR) AF: 0.479 AC: 13268 AN: 27722

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 10541 AN: 17054

East Asian (EAS) AF: 0.492 AC: 16243 AN: 33010

South Asian (SAS) AF: 0.302 AC: 16984 AN: 56174

European-Finnish (FIN) AF: 0.578 AC: 27350 AN: 47318

Middle Eastern (MID) AF: 0.567 AC: 1581 AN: 2788

European-Non Finnish (NFE) AF: 0.665 AC: 294899 AN: 443498

Other (OTH) AF: 0.576 AC: 19294 AN: 33502

GnomAD4 genome AF: 0.484 AC: 73595 AN: 152004 Hom.: 21074 Cov.: 31 AF XY: 0.477 AC XY: 35427 AN XY: 74272

African (AFR) AF: 0.175 AC: 7276 AN: 41486

American (AMR) AF: 0.511 AC: 7793 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2097 AN: 3470

East Asian (EAS) AF: 0.514 AC: 2648 AN: 5150

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4812

European-Finnish (FIN) AF: 0.569 AC: 6006 AN: 10548

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44506 AN: 67976

Other (OTH) AF: 0.509 AC: 1074 AN: 2108

Alfa AF: 0.592 Hom.: 35796

Bravo AF: 0.476

Asia WGS AF: 0.375 AC: 1308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.40
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3765066; hg19: chr15-75140854;