1-155256732-A-C

Variant names:

• chr1-155256732-A-C
• rs201183243
• NM_005698.4:c.839T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005698.4(SCAMP3):​c.839T>G​(p.Leu280Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. L280P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCAMP3 NM_005698.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.11

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAMP3	NM_005698.4	c.839T>G	p.Leu280Arg	missense_variant	Exon 8 of 9	ENST00000302631.8	NP_005689.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAMP3	ENST00000302631.8	c.839T>G	p.Leu280Arg	missense_variant	Exon 8 of 9	1	NM_005698.4	ENSP00000307275.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251430 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135898

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.97	D;D
Vest4		0.70
MutPred		0.78		Gain of methylation at L280 (P = 0.0217);.;
MVP		0.72
MPC		1.1
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.80
gMVP		0.92

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

LitVar

Other links and lift over

dbSNP: rs201183243; hg19: chr1-155226523;