15-74854038-T-A

Variant names:

• chr15-74854038-T-A
• rs75280463
• NM_005697.5:c.208A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005697.5(SCAMP2):​c.208A>T​(p.Thr70Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,614,058 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (33 hom.)
• Consequence: SCAMP2 NM_005697.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0350
• Publications: 8 publications found

Genes affected

SCAMP2 (HGNC:10564): (secretory carrier membrane protein 2) This gene product belongs to the SCAMP family of proteins which are secretory carrier membrane proteins. They function as carriers to the cell surface in post-golgi recycling pathways. Different family members are highly related products of distinct genes, and are usually expressed together. These findings suggest that the SCAMPs may function at the same site during vesicular transport rather than in separate pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038162172).
• BP6: Variant 15-74854038-T-A is Benign according to our data. Variant chr15-74854038-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2645551.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005697.5. 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
	SCAMP2	NM_005697.5	MANE Select	c.208A>T	p.Thr70Ser	missense	Exon 3 of 9	NP_005688.2
	SCAMP2	NM_001320778.2		c.208A>T	p.Thr70Ser	missense	Exon 3 of 10	NP_001307707.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAMP2	ENST00000268099.13	TSL:1 MANE Select	c.208A>T	p.Thr70Ser	missense	Exon 3 of 9	ENSP00000268099.9	O15127
	SCAMP2	ENST00000894365.1		c.208A>T	p.Thr70Ser	missense	Exon 3 of 10	ENSP00000564424.1
	SCAMP2	ENST00000960462.1		c.208A>T	p.Thr70Ser	missense	Exon 3 of 9	ENSP00000630521.1

Frequencies

GnomAD3 genomes AF: 0.00346 AC: 527 AN: 152204 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00589

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00316 AC: 795 AN: 251384 AF XY: 0.00322

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000786

Gnomad NFE exome AF: 0.00570

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00605 AC: 8837 AN: 1461736 Hom.: 33 Cov.: 31 AF XY: 0.00585 AC XY: 4252 AN XY: 727184

African (AFR) AF: 0.000986 AC: 33 AN: 33478

American (AMR) AF: 0.00246 AC: 110 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000612 AC: 16 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86254

European-Finnish (FIN) AF: 0.00109 AC: 58 AN: 53420

Middle Eastern (MID) AF: 0.000700 AC: 4 AN: 5716

European-Non Finnish (NFE) AF: 0.00737 AC: 8192 AN: 1111928

Other (OTH) AF: 0.00679 AC: 410 AN: 60386

GnomAD4 genome AF: 0.00346 AC: 527 AN: 152322 Hom.: 3 Cov.: 33 AF XY: 0.00322 AC XY: 240 AN XY: 74478

African (AFR) AF: 0.00115 AC: 48 AN: 41564

American (AMR) AF: 0.00379 AC: 58 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00590 AC: 401 AN: 68020

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00548 Hom.: 2

Bravo AF: 0.00379

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00733 AC: 63

ExAC AF: 0.00308 AC: 374

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00583

EpiControl AF: 0.00688

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.0
DANN	Benign	0.83
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.59
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.035
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.016
Sift	Benign	0.43	T
Sift4G	Benign	0.67	T
Polyphen		0.018	B
Vest4		0.25
MutPred		0.23		Loss of glycosylation at T70 (P = 0.0863)
MVP		0.30
MPC		0.33
ClinPred		0.0015	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.19
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs75280463; hg19: chr15-75146379; COSMIC: COSV99174021; COSMIC: COSV99174021;