Variant 15-51689327-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013243.4(SCG3):c.649A>G(p.Ser217Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SCG3
NM_013243.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

SCG3 (HGNC:13707): (secretogranin III) The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. Granins may serve as precursors for biologically active peptides. Some granins have been shown to function as helper proteins in sorting and proteolytic processing of prohormones; however, the function of this protein is unknown. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

SCG3 links:

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ACMG classification

Classification made for transcript

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=0.14234507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCG3	NM_013243.4 linkuse as main transcript	c.649A>G	p.Ser217Gly	missense_variant	6/12	ENST00000220478.8
SCG3	NM_001165257.2 linkuse as main transcript	c.-48A>G		5_prime_UTR_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCG3	ENST00000220478.8 linkuse as main transcript	c.649A>G	p.Ser217Gly	missense_variant	6/12	1	NM_013243.4	P1	Q8WXD2-1
SCG3	ENST00000542355.6 linkuse as main transcript	c.-48A>G		5_prime_UTR_variant	5/11	2			Q8WXD2-2
SCG3	ENST00000558709.1 linkuse as main transcript	c.-48A>G		5_prime_UTR_variant	4/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251106

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00000479

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727174

show subpopulations

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

The c.649A>G (p.S217G) alteration is located in exon 6 (coding exon 6) of the SCG3 gene. This alteration results from a A to G substitution at nucleotide position 649, causing the serine (S) at amino acid position 217 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.086

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.061

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.54

M_CAP

Benign

0.013

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

0.85

D;D

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.6

REVEL

Benign

0.079

Sift

Uncertain

0.028

Sift4G

Benign

0.64

Polyphen

0.17

Vest4

0.39

MutPred

0.11

Gain of methylation at K214 (P = 0.0954);

MVP

0.072

MPC

0.19

ClinPred

0.26

GERP RS

5.9

Varity_R

0.083

gMVP

0.081

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over