1-155260595-T-G

Variant names:

• chr1-155260595-T-G
• NM_005698.4:c.209A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005698.4(SCAMP3):​c.209A>C​(p.Gln70Pro) 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. 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: 3.01

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15497452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAMP3	NM_005698.4	c.209A>C	p.Gln70Pro	missense_variant	Exon 3 of 9	ENST00000302631.8	NP_005689.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAMP3	ENST00000302631.8	c.209A>C	p.Gln70Pro	missense_variant	Exon 3 of 9	1	NM_005698.4	ENSP00000307275.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.209A>C (p.Q70P) alteration is located in exon 3 (coding exon 3) of the SCAMP3 gene. This alteration results from a A to C substitution at nucleotide position 209, causing the glutamine (Q) at amino acid position 70 to be replaced by a proline (P). 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	0.056
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.034	T;.
Eigen	Benign	0.037
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.7	D;N
REVEL	Benign	0.11
Sift	Benign	0.097	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.0	B;D
Vest4		0.44
MutPred		0.20		Gain of glycosylation at Q70 (P = 0.0148);.;
MVP		0.35
MPC		0.32
ClinPred		0.60	D
GERP RS		3.6
Varity_R		0.27
gMVP		0.51

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: chr1-155230386;