chr1-155256413-A-C

Position:

• chr1-155256413-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005698.4(SCAMP3):​c.904T>G​(p.Ser302Ala) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAMP3 NM_005698.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.10

Genes affected

SCAMP3 (HGNC:10565): (secretory carrier membrane protein 3) This gene encodes an integral membrane protein that belongs to the secretory carrier membrane protein family. The encoded protein functions as a carrier to the cell surface in post-golgi recycling pathways. This protein is also involved in protein trafficking in endosomal pathways. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28713685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCAMP3	NM_005698.4	c.904T>G	p.Ser302Ala	missense_variant	9/9	ENST00000302631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAMP3	ENST00000302631.8	c.904T>G	p.Ser302Ala	missense_variant	9/9	1	NM_005698.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2021

The c.904T>G (p.S302A) alteration is located in exon 9 (coding exon 9) of the SCAMP3 gene. This alteration results from a T to G substitution at nucleotide position 904, causing the serine (S) at amino acid position 302 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	0.014
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.082
Sift	Benign	0.22	T;T
Sift4G	Benign	0.52	T;T
Polyphen		1.0	D;B
Vest4		0.52
MutPred		0.52		Loss of disorder (P = 0.0975);.;
MVP		0.28
MPC		0.83
ClinPred		0.79	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-155226204;