chr15-74854038-T-G

Variant names:

• chr15-74854038-T-G
• rs75280463
• NM_005697.5:c.208A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005697.5(SCAMP2):​c.208A>C​(p.Thr70Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. T70S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCAMP2 NM_005697.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042192668).

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.208A>C	p.Thr70Pro	missense	Exon 3 of 9	NP_005688.2
	SCAMP2	NM_001320778.2		c.208A>C	p.Thr70Pro	missense	Exon 3 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.208A>C	p.Thr70Pro	missense	Exon 3 of 9	ENSP00000268099.9	O15127
	SCAMP2	ENST00000894365.1		c.208A>C	p.Thr70Pro	missense	Exon 3 of 10	ENSP00000564424.1
	SCAMP2	ENST00000960462.1		c.208A>C	p.Thr70Pro	missense	Exon 3 of 9	ENSP00000630521.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.48	N
PhyloP100		0.035
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.020
Sift	Benign	0.44	T
Sift4G	Benign	0.48	T
Polyphen		0.38	B
Vest4		0.28
MutPred		0.23		Gain of catalytic residue at P69 (P = 0.0119)
MVP		0.36
MPC		0.48
ClinPred		0.39	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.080
gMVP		0.20
Mutation Taster		=71/29	polymorphism

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: rs75280463; hg19: chr15-75146379;