chr15-75018840-G-A

Position:

• chr15-75018840-G-A

Variant summary

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

The NM_138967.4(SCAMP5):​c.565G>A​(p.Glu189Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SCAMP5 NM_138967.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.61

Genes affected

SCAMP5 (HGNC:30386): (secretory carrier membrane protein 5) Involved in positive regulation of cytokine production; regulation of vesicle-mediated transport; and response to endoplasmic reticulum stress. Located in Golgi apparatus; plasma membrane; and recycling endosome membrane. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SCAMP5 (HGNC:):

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, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAMP5	NM_138967.4	c.565G>A	p.Glu189Lys	missense_variant	7/7	ENST00000425597.8	NP_620417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAMP5	ENST00000425597.8	c.565G>A	p.Glu189Lys	missense_variant	7/7	1	NM_138967.4	ENSP00000406547.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Mar 04, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.59	D;.;D;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	.;D;D;D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	3.5	M;.;M;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.7	D;D;D;D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.82
MutPred		0.75		Gain of MoRF binding (P = 9e-04);.;Gain of MoRF binding (P = 9e-04);.;
MVP		0.77
MPC		1.8
ClinPred		1.0	D
GERP RS		4.2
Varity_R		0.86
gMVP		1.0

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: chr15-75311181; COSMIC: COSV61625017; COSMIC: COSV61625017;