15-74854991-A-C

Variant names:

• chr15-74854991-A-C
• rs1869959
• NM_005697.5:c.58-342T>G

Variant summary

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

The NM_005697.5(SCAMP2):​c.58-342T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 144,702 control chromosomes in the GnomAD database, including 33,202 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 0.68 (33202 hom., cov: 24)
• Consequence: SCAMP2 NM_005697.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 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.58-342T>G		intron	N/A	NP_005688.2
	SCAMP2	NM_001320778.2		c.58-342T>G		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.58-342T>G		intron	N/A	ENSP00000268099.9
	SCAMP2	ENST00000564529.1	TSL:2	c.58-342T>G		intron	N/A	ENSP00000457564.1
	SCAMP2	ENST00000562363.5	TSL:5	c.58-872T>G		intron	N/A	ENSP00000457890.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 98667 AN: 144644 Hom.: 33190 Cov.: 24

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.674

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.682 AC: 98705 AN: 144702 Hom.: 33202 Cov.: 24 AF XY: 0.681 AC XY: 47794 AN XY: 70138

African (AFR) AF: 0.619 AC: 23863 AN: 38556

American (AMR) AF: 0.692 AC: 10119 AN: 14632

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2315 AN: 3426

East Asian (EAS) AF: 0.739 AC: 3688 AN: 4988

South Asian (SAS) AF: 0.683 AC: 3068 AN: 4494

European-Finnish (FIN) AF: 0.693 AC: 6237 AN: 8996

Middle Eastern (MID) AF: 0.728 AC: 211 AN: 290

European-Non Finnish (NFE) AF: 0.710 AC: 47149 AN: 66410

Other (OTH) AF: 0.674 AC: 1355 AN: 2010

Alfa AF: 0.464 Hom.: 621

Bravo AF: 0.669

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.066
DANN	Benign	0.33
PhyloP100		-2.1
PromoterAI		-0.016	Neutral
Mutation Taster		=9/91	disease causing (long InDel)

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: rs1869959; hg19: chr15-75147332;