chr15-32679733-C-T

Position:

• chr15-32679733-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001144757.3(SCG5):​c.227-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,606,720 control chromosomes in the GnomAD database, including 56,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5554 hom., cov: 32)
  • Exomes 𝑓: 0.25 (50460 hom.)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0700

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-32679733-C-T is Benign according to our data. Variant chr15-32679733-C-T is described in ClinVar as [Benign]. Clinvar id is 1239157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.227-33C>T		intron_variant		ENST00000300175.9	NP_001138229.1
ARHGAP11A-SCG5	NM_001368319.1	c.1469-33C>T		intron_variant			NP_001355248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.227-33C>T		intron_variant		1	NM_001144757.3	ENSP00000300175	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39083 AN: 151948 Hom.: 5552 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.260

GnomAD3 exomes AF: 0.299 AC: 74352 AN: 248296 Hom.: 12705 AF XY: 0.301 AC XY: 40584 AN XY: 134672

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.587

Gnomad SAS exome AF: 0.412

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.249 AC: 362631 AN: 1454654 Hom.: 50460 Cov.: 31 AF XY: 0.254 AC XY: 183623 AN XY: 723890

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.589

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.257 AC: 39102 AN: 152066 Hom.: 5554 Cov.: 32 AF XY: 0.269 AC XY: 19990 AN XY: 74326

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.260

Alfa AF: 0.230 Hom.: 7385

Bravo AF: 0.245

Asia WGS AF: 0.486 AC: 1687 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.3
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs7177843; hg19: chr15-32971934;