rs16964476

Positions:

• chr15-51682027-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013243.4(SCG3):​c.82+190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0524 in 152,236 control chromosomes in the GnomAD database, including 570 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.052 (570 hom., cov: 32)
• Consequence: SCG3 NM_013243.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCG3	NM_013243.4	c.82+190A>G		intron_variant		ENST00000220478.8	NP_037375.2
SCG3	NM_001165257.2	c.-562+190A>G		intron_variant			NP_001158729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCG3	ENST00000220478.8	c.82+190A>G		intron_variant		1	NM_013243.4	ENSP00000220478	P1
SCG3	ENST00000542355.6	c.-562+190A>G		intron_variant		2		ENSP00000445205
SCG3	ENST00000558709.1	c.-419+190A>G		intron_variant		2		ENSP00000452745

Frequencies

GnomAD3 genomes AF: 0.0523 AC: 7963 AN: 152118 Hom.: 570 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0952

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0373

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0524 AC: 7980 AN: 152236 Hom.: 570 Cov.: 32 AF XY: 0.0518 AC XY: 3853 AN XY: 74444

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0228

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0950

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.00828 Hom.: 125

Bravo AF: 0.0591

Asia WGS AF: 0.0520 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16964476; hg19: chr15-51974224; COSMIC: COSV55022871;