chr15-32643947-T-C

Position:

• chr15-32643947-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001144757.3(SCG5):​c.226+129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 743,398 control chromosomes in the GnomAD database, including 3,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.075 (559 hom., cov: 32)
  • Exomes 𝑓: 0.092 (2820 hom.)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.656

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-32643947-T-C is Benign according to our data. Variant chr15-32643947-T-C is described in ClinVar as [Benign]. Clinvar id is 1244454.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.226+129T>C		intron_variant		ENST00000300175.9	NP_001138229.1
ARHGAP11A-SCG5	NM_001368319.1	c.1468+129T>C		intron_variant			NP_001355248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.226+129T>C		intron_variant		1	NM_001144757.3	ENSP00000300175	P1

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11400 AN: 152132 Hom.: 559 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0928

GnomAD4 exome AF: 0.0918 AC: 54290 AN: 591148 Hom.: 2820 AF XY: 0.0891 AC XY: 27233 AN XY: 305584

Gnomad4 AFR exome AF: 0.0197

Gnomad4 AMR exome AF: 0.0806

Gnomad4 ASJ exome AF: 0.0806

Gnomad4 EAS exome AF: 0.0000939

Gnomad4 SAS exome AF: 0.0316

Gnomad4 FIN exome AF: 0.0977

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.0859

GnomAD4 genome AF: 0.0749 AC: 11398 AN: 152250 Hom.: 559 Cov.: 32 AF XY: 0.0740 AC XY: 5511 AN XY: 74428

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.0867

Gnomad4 ASJ AF: 0.0779

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0327

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0923

Alfa AF: 0.0931 Hom.: 188

Bravo AF: 0.0726

Asia WGS AF: 0.0170 AC: 61 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.66
DANN	Benign	0.70

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: rs72715242; hg19: chr15-32936148;