NM_005697.5:c.226-571A>G

Variant names:

• chr15-74852757-T-C
• rs936230
• NM_005697.5:c.226-571A>G

Variant summary

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

The NM_005697.5(SCAMP2):​c.226-571A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,594 control chromosomes in the GnomAD database, including 33,941 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 0.66 (33823 hom., cov: 33)
  • Exomes 𝑓: 0.68 (118 hom.)
• Consequence: SCAMP2 NM_005697.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAMP2	NM_005697.5	c.226-571A>G		intron_variant	Intron 3 of 8	ENST00000268099.13	NP_005688.2
SCAMP2	NM_001320778.2	c.355-571A>G		intron_variant	Intron 4 of 9		NP_001307707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAMP2	ENST00000268099.13	c.226-571A>G		intron_variant	Intron 3 of 8	1	NM_005697.5	ENSP00000268099.9

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101011 AN: 152008 Hom.: 33789 Cov.: 33

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.675 AC: 316 AN: 468 Hom.: 118 Cov.: 0 AF XY: 0.667 AC XY: 216 AN XY: 324

Gnomad4 AFR exome AF: 0.600

Gnomad4 AMR exome AF: 0.833

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.571

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.692

GnomAD4 genome AF: 0.665 AC: 101096 AN: 152126 Hom.: 33823 Cov.: 33 AF XY: 0.663 AC XY: 49267 AN XY: 74360

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.660

Alfa AF: 0.672 Hom.: 5469

Bravo AF: 0.665

Asia WGS AF: 0.729 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.1
DANN	Benign	0.50

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: rs936230; hg19: chr15-75145098;