chr15-75012709-T-G

Position:

• chr15-75012709-T-G

Variant summary

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

The NM_138967.4(SCAMP5):​c.40T>G​(p.Phe14Val) 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: 32)
• Consequence: SCAMP5 NM_138967.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

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, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAMP5	NM_138967.4	c.40T>G	p.Phe14Val	missense_variant	3/7	ENST00000425597.8	NP_620417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAMP5	ENST00000425597.8	c.40T>G	p.Phe14Val	missense_variant	3/7	1	NM_138967.4	ENSP00000406547.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 10, 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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.;T;.;T;.;T;.;T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	.;T;T;T;T;T;D;T;T;T
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.3	M;.;.;M;.;.;M;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-4.0	D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.35
Sift	Benign	0.058	T;T;T;T;T;T;T;D;T;T
Sift4G	Benign	0.17	T;T;T;T;T;T;T;T;T;T
Polyphen		0.99	D;.;.;P;.;.;D;.;.;.
Vest4		0.69
MutPred		0.75		Gain of ubiquitination at K13 (P = 0.1696);Gain of ubiquitination at K13 (P = 0.1696);Gain of ubiquitination at K13 (P = 0.1696);Gain of ubiquitination at K13 (P = 0.1696);Gain of ubiquitination at K13 (P = 0.1696);Gain of ubiquitination at K13 (P = 0.1696);Gain of ubiquitination at K13 (P = 0.1696);Gain of ubiquitination at K13 (P = 0.1696);Gain of ubiquitination at K13 (P = 0.1696);Gain of ubiquitination at K13 (P = 0.1696);
MVP		0.63
MPC		1.8
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.40
gMVP		0.96

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: chr15-75305050;