rs12438604

Positions:

• chr15-32680796-C-A
• chr15-32680796-C-T

Variant summary

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

The NM_001144757.3(SCG5):​c.376+881C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,936 control chromosomes in the GnomAD database, including 5,531 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 0.26 (5531 hom., cov: 31)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467

Genes affected

SCG5 (HGNC:10816): (secretogranin V) This gene encodes a secreted chaperone protein that prevents the aggregation of other secreted proteins, including proteins that are associated with neurodegenerative and metabolic disease. The encoded protein may be best known for its role in the trafficking and activation of prohormone convertase PC2 (encoded by Gene ID: 5126). Phosphorylation of the encoded protein has been shown to have an inhibitory effect on its chaperone function. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

ARHGAP11A-SCG5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCG5	NM_001144757.3	c.376+881C>A		intron_variant		ENST00000300175.9
ARHGAP11A-SCG5	NM_001368319.1	c.1618+881C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCG5	ENST00000300175.9	c.376+881C>A		intron_variant		1	NM_001144757.3	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39004 AN: 151818 Hom.: 5528 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.257 AC: 39024 AN: 151936 Hom.: 5531 Cov.: 31 AF XY: 0.269 AC XY: 19942 AN XY: 74252

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.262

Alfa AF: 0.237 Hom.: 2564

Bravo AF: 0.245

Asia WGS AF: 0.487 AC: 1689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12438604; hg19: chr15-32972997;