chr15-32679557-G-A

Position:

• chr15-32679557-G-A

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.227-209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,990 control chromosomes in the GnomAD database, including 26,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.58 (26970 hom., cov: 32)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.45

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=-0.91).
• BP6: Variant 15-32679557-G-A is Benign according to our data. Variant chr15-32679557-G-A is described in ClinVar as [Benign]. Clinvar id is 1267827.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.227-209G>A		intron_variant		ENST00000300175.9	NP_001138229.1
ARHGAP11A-SCG5	NM_001368319.1	c.1469-209G>A		intron_variant			NP_001355248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.227-209G>A		intron_variant		1	NM_001144757.3	ENSP00000300175	P1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88765 AN: 151872 Hom.: 26961 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.584 AC: 88799 AN: 151990 Hom.: 26970 Cov.: 32 AF XY: 0.575 AC XY: 42675 AN XY: 74272

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.597

Alfa AF: 0.671 Hom.: 71182

Bravo AF: 0.592

Asia WGS AF: 0.434 AC: 1514 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 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0060
DANN	Benign	0.38

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: rs3817592; hg19: chr15-32971758;