rs750946574

Variant names:

• chr1-155256419-T-C
• rs750946574
• NM_005698.4:c.898A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001438466.1(SCAMP3):​c.930A>G​(p.Ter310Trpext*?) variant causes a stop lost, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000771 in 1,426,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000077 (0 hom.)
• Consequence: SCAMP3 NM_001438466.1 stop_lost, splice_region
• Scores: Splicing: ADA: 0.0005599
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• Publications: 1 publications found

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]

ENSG00000303088 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Stoplost variant in NM_001438466.1 Downstream stopcodon found after 95 codons.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438466.1. 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
	SCAMP3	NM_005698.4	MANE Select	c.898A>G	p.Ile300Val	missense splice_region	Exon 9 of 9	NP_005689.2
	SCAMP3	NM_001438464.1		c.856A>G	p.Ile286Val	missense splice_region	Exon 9 of 9	NP_001425393.1
	SCAMP3	NM_052837.3		c.820A>G	p.Ile274Val	missense splice_region	Exon 8 of 8	NP_443069.1	O14828-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAMP3	ENST00000302631.8	TSL:1 MANE Select	c.898A>G	p.Ile300Val	missense splice_region	Exon 9 of 9	ENSP00000307275.3	O14828-1
	SCAMP3	ENST00000355379.3	TSL:1	c.820A>G	p.Ile274Val	missense splice_region	Exon 8 of 8	ENSP00000347540.3	O14828-2
	SCAMP3	ENST00000880568.1		c.916A>G	p.Ile306Val	missense splice_region	Exon 9 of 9	ENSP00000550627.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000446 AC: 1 AN: 224050 AF XY: 0.00000825

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000978

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000771 AC: 11 AN: 1426176 Hom.: 0 Cov.: 31 AF XY: 0.00000850 AC XY: 6 AN XY: 705548

African (AFR) AF: 0.00 AC: 0 AN: 32278

American (AMR) AF: 0.00 AC: 0 AN: 39484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24170

East Asian (EAS) AF: 0.00 AC: 0 AN: 39200

South Asian (SAS) AF: 0.00 AC: 0 AN: 82748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52514

Middle Eastern (MID) AF: 0.000538 AC: 3 AN: 5580

European-Non Finnish (NFE) AF: 0.00000733 AC: 8 AN: 1091492

Other (OTH) AF: 0.00 AC: 0 AN: 58710

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.67
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.80	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.32	N
PhyloP100		1.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.096
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.24	B
Vest4		0.14
MutPred		0.54		Loss of catalytic residue at I300 (P = 0.0815)
MVP		0.27
MPC		0.35
ClinPred		0.12	T
GERP RS		5.1
Varity_R		0.077
gMVP		0.51
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00056
dbscSNV1_RF	Benign	0.042
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: rs750946574; hg19: chr1-155226210;