rs377025082

Variant names:

• chr15-74852122-G-A
• rs377025082
• NM_005697.5:c.290C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-74852122-G-A
• chr15-74852122-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005697.5(SCAMP2):​c.290C>T​(p.Ala97Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,440,022 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A97G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SCAMP2 NM_005697.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.90

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAMP2	NM_005697.5	c.290C>T	p.Ala97Val	missense_variant	Exon 4 of 9	ENST00000268099.13	NP_005688.2
SCAMP2	NM_001320778.2	c.419C>T	p.Ala140Val	missense_variant	Exon 5 of 10		NP_001307707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAMP2	ENST00000268099.13	c.290C>T	p.Ala97Val	missense_variant	Exon 4 of 9	1	NM_005697.5	ENSP00000268099.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440022 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715926

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000238

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.0092	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.23	T;T;.;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.020	D;D;D;D
Sift4G	Benign	0.062	T;D;.;.
Polyphen		0.98	D;.;.;.
Vest4		0.55
MutPred		0.26		Gain of helix (P = 0.0082);.;.;.;
MVP		0.62
MPC		0.95
ClinPred		0.97	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.36
gMVP		0.61

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: rs377025082; hg19: chr15-75144463;