15-75016309-C-T

Variant names:

• chr15-75016309-C-T
• rs4886414
• NM_138967.4:c.137-284C>T

Variant summary

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

The NM_138967.4(SCAMP5):​c.137-284C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,944 control chromosomes in the GnomAD database, including 25,908 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 0.53 (25908 hom., cov: 31)
• Consequence: SCAMP5 NM_138967.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 6 publications found

Genes affected

SCAMP5 (HGNC:30386): (secretory carrier membrane protein 5) Involved in positive regulation of cytokine production; regulation of vesicle-mediated transport; and response to endoplasmic reticulum stress. Located in Golgi apparatus; plasma membrane; and recycling endosome membrane. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SCAMP5 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina
• epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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 (NFE) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138967.4. 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
	SCAMP5	NM_138967.4	MANE Select	c.137-284C>T		intron	N/A	NP_620417.1
	SCAMP5	NM_001178111.2		c.137-284C>T		intron	N/A	NP_001171582.1
	SCAMP5	NM_001178112.2		c.137-284C>T		intron	N/A	NP_001171583.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAMP5	ENST00000425597.8	TSL:1 MANE Select	c.137-284C>T		intron	N/A	ENSP00000406547.3
	SCAMP5	ENST00000562212.5	TSL:1	c.137-284C>T		intron	N/A	ENSP00000455313.1
	SCAMP5	ENST00000912850.1		c.137-284C>T		intron	N/A	ENSP00000582909.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80010 AN: 151826 Hom.: 25907 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.527 AC: 80025 AN: 151944 Hom.: 25908 Cov.: 31 AF XY: 0.521 AC XY: 38734 AN XY: 74276

African (AFR) AF: 0.164 AC: 6809 AN: 41420

American (AMR) AF: 0.576 AC: 8789 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2071 AN: 3464

East Asian (EAS) AF: 0.262 AC: 1347 AN: 5148

South Asian (SAS) AF: 0.332 AC: 1599 AN: 4812

European-Finnish (FIN) AF: 0.712 AC: 7524 AN: 10574

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50018 AN: 67964

Other (OTH) AF: 0.519 AC: 1096 AN: 2110

Alfa AF: 0.657 Hom.: 88753

Bravo AF: 0.506

Asia WGS AF: 0.251 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.67
DANN	Benign	0.54
PhyloP100		0.056
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: rs4886414; hg19: chr15-75308650; COSMIC: COSV62643613; COSMIC: COSV62643613;