15-74854991-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005697.5(SCAMP2):​c.58-342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 144,802 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000021 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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>C		intron	N/A	NP_005688.2
	SCAMP2	NM_001320778.2		c.58-342T>C		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>C		intron	N/A	ENSP00000268099.9
	SCAMP2	ENST00000564529.1	TSL:2	c.58-342T>C		intron	N/A	ENSP00000457564.1
	SCAMP2	ENST00000562363.5	TSL:5	c.58-872T>C		intron	N/A	ENSP00000457890.1

Frequencies

GnomAD3 genomes AF: 0.0000207 AC: 3 AN: 144744 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000222

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000207 AC: 3 AN: 144802 Hom.: 0 Cov.: 24 AF XY: 0.0000285 AC XY: 2 AN XY: 70204

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000259 AC: 1 AN: 38594

American (AMR) AF: 0.00 AC: 0 AN: 14640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 4990

South Asian (SAS) AF: 0.00 AC: 0 AN: 4494

European-Finnish (FIN) AF: 0.000222 AC: 2 AN: 9010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66438

Other (OTH) AF: 0.00 AC: 0 AN: 2016

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000416442), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 621

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.074
DANN	Benign	0.78
PhyloP100		-2.1
PromoterAI		0.037	Neutral

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;