1-155258951-C-T

Variant names:

• chr1-155258951-C-T
• rs143130366
• NM_005698.4:c.392G>A

Variant summary

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

The NM_005698.4(SCAMP3):​c.392G>A​(p.Arg131Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000547 in 1,608,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R131P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00058 (0 hom.)
• Consequence: SCAMP3 NM_005698.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26

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=0.12688822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAMP3	NM_005698.4	c.392G>A	p.Arg131Gln	missense_variant	Exon 5 of 9	ENST00000302631.8	NP_005689.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAMP3	ENST00000302631.8	c.392G>A	p.Arg131Gln	missense_variant	Exon 5 of 9	1	NM_005698.4	ENSP00000307275.3

Frequencies

GnomAD3 genomes AF: 0.000271 AC: 41 AN: 151210 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000471

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000202 AC: 50 AN: 246918 Hom.: 0 AF XY: 0.000157 AC XY: 21 AN XY: 133650

Gnomad AFR exome AF: 0.000250

Gnomad AMR exome AF: 0.0000298

Gnomad ASJ exome AF: 0.000402

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000336

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000348

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000576 AC: 839 AN: 1457310 Hom.: 0 Cov.: 31 AF XY: 0.000542 AC XY: 393 AN XY: 724960

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.000423

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000718

Gnomad4 OTH exome AF: 0.000332

GnomAD4 genome AF: 0.000271 AC: 41 AN: 151210 Hom.: 0 Cov.: 29 AF XY: 0.000217 AC XY: 16 AN XY: 73726

Gnomad4 AFR AF: 0.000146

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000223

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.000439

EpiControl AF: 0.000300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.043	T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.12
Sift	Benign	0.21	T;T
Sift4G	Benign	0.27	T;T
Polyphen		1.0	D;P
Vest4		0.30
MVP		0.38
MPC		0.45
ClinPred		0.11	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs143130366; hg19: chr1-155228742; COSMIC: COSV56944515; COSMIC: COSV56944515;