15-74844353-T-C

Variant names:

• chr15-74844353-T-C
• rs12487
• NM_005697.5:c.*730A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005697.5(SCAMP2):​c.*730A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,092 control chromosomes in the GnomAD database, including 12,636 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 0.35 (12622 hom., cov: 31)
  • Exomes 𝑓: 0.48 (14 hom.)
• Consequence: SCAMP2 NM_005697.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAMP2	NM_005697.5	c.*730A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000268099.13	NP_005688.2
SCAMP2	NM_001320778.2	c.*730A>G		3_prime_UTR_variant	Exon 10 of 10		NP_001307707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAMP2	ENST00000268099	c.*730A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_005697.5	ENSP00000268099.9
SCAMP2	ENST00000566480	c.*1018A>G		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000455377.1
SCAMP2	ENST00000563663.5	n.*924A>G		non_coding_transcript_exon_variant	Exon 4 of 4	5		ENSP00000455963.1
SCAMP2	ENST00000563663.5	n.*924A>G		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000455963.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53793 AN: 151842 Hom.: 12627 Cov.: 31

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.477 AC: 63 AN: 132 Hom.: 14 Cov.: 0 AF XY: 0.480 AC XY: 47 AN XY: 98

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.354 AC: 53784 AN: 151960 Hom.: 12622 Cov.: 31 AF XY: 0.343 AC XY: 25466 AN XY: 74282

Gnomad4 AFR AF: 0.0971

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.0690

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.348

Alfa AF: 0.403 Hom.: 2861

Bravo AF: 0.337

Asia WGS AF: 0.103 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.80
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs12487; hg19: chr15-75136694;