chr15-74854594-T-G

Variant names:

• chr15-74854594-T-G
• rs1157771503
• NM_005697.5:c.113A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005697.5(SCAMP2):​c.113A>C​(p.Asn38Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. N38S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCAMP2 NM_005697.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41771066).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAMP2	NM_005697.5	MANE Select	c.113A>C	p.Asn38Thr	missense	Exon 2 of 9	NP_005688.2
	SCAMP2	NM_001320778.2		c.113A>C	p.Asn38Thr	missense	Exon 2 of 10	NP_001307707.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAMP2	ENST00000268099.13	TSL:1 MANE Select	c.113A>C	p.Asn38Thr	missense	Exon 2 of 9	ENSP00000268099.9	O15127
	SCAMP2	ENST00000894365.1		c.113A>C	p.Asn38Thr	missense	Exon 2 of 10	ENSP00000564424.1
	SCAMP2	ENST00000960462.1		c.113A>C	p.Asn38Thr	missense	Exon 2 of 9	ENSP00000630521.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.96	P
Vest4		0.55
MutPred		0.42		Gain of glycosylation at N38 (P = 0.019)
MVP		0.69
MPC		0.98
ClinPred		0.99	D
GERP RS		5.8
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.72
gMVP		0.69

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: rs1157771503; hg19: chr15-75146935;