15-32680053-G-A

Position:

• chr15-32680053-G-A

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.376+138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 774,472 control chromosomes in the GnomAD database, including 1,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (236 hom., cov: 32)
  • Exomes 𝑓: 0.055 (1231 hom.)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0190

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=-0.87).
• BP6: Variant 15-32680053-G-A is Benign according to our data. Variant chr15-32680053-G-A is described in ClinVar as [Benign]. Clinvar id is 1236383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.376+138G>A		intron_variant		ENST00000300175.9	NP_001138229.1
ARHGAP11A-SCG5	NM_001368319.1	c.1618+138G>A		intron_variant			NP_001355248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.376+138G>A		intron_variant		1	NM_001144757.3	ENSP00000300175	P1

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7159 AN: 152122 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.0581

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0698

Gnomad OTH AF: 0.0479

GnomAD4 exome AF: 0.0550 AC: 34193 AN: 622232 Hom.: 1231 AF XY: 0.0535 AC XY: 17269 AN XY: 322578

Gnomad4 AFR exome AF: 0.0173

Gnomad4 AMR exome AF: 0.0390

Gnomad4 ASJ exome AF: 0.0374

Gnomad4 EAS exome AF: 0.0000882

Gnomad4 SAS exome AF: 0.00718

Gnomad4 FIN exome AF: 0.0523

Gnomad4 NFE exome AF: 0.0680

Gnomad4 OTH exome AF: 0.0522

GnomAD4 genome AF: 0.0470 AC: 7159 AN: 152240 Hom.: 236 Cov.: 32 AF XY: 0.0453 AC XY: 3371 AN XY: 74452

Gnomad4 AFR AF: 0.0179

Gnomad4 AMR AF: 0.0498

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00871

Gnomad4 FIN AF: 0.0581

Gnomad4 NFE AF: 0.0698

Gnomad4 OTH AF: 0.0474

Alfa AF: 0.0569 Hom.: 39

Bravo AF: 0.0457

Asia WGS AF: 0.00635 AC: 22 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	-0.87
CADD	Benign	1.9
DANN	Benign	0.62

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: rs75242289; hg19: chr15-32972254;