15-32691995-A-G

Position:

• chr15-32691995-A-G

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.543+232A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 1,382,240 control chromosomes in the GnomAD database, including 651,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66416 hom., cov: 31)
  • Exomes 𝑓: 0.98 (585554 hom.)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.237

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=-0.91).
• BP6: Variant 15-32691995-A-G is Benign according to our data. Variant chr15-32691995-A-G is described in ClinVar as [Benign]. Clinvar id is 1227945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.543+232A>G		intron_variant		ENST00000300175.9	NP_001138229.1
ARHGAP11A-SCG5	NM_001368319.1	c.1782+232A>G		intron_variant			NP_001355248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.543+232A>G		intron_variant		1	NM_001144757.3	ENSP00000300175	P1

Frequencies

GnomAD3 genomes AF: 0.932 AC: 141794 AN: 152090 Hom.: 66378 Cov.: 31

Gnomad AFR AF: 0.833

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.978

Gnomad OTH AF: 0.941

GnomAD4 exome AF: 0.975 AC: 1199778 AN: 1230032 Hom.: 585554 Cov.: 42 AF XY: 0.975 AC XY: 576416 AN XY: 590988

Gnomad4 AFR exome AF: 0.827

Gnomad4 AMR exome AF: 0.972

Gnomad4 ASJ exome AF: 0.964

Gnomad4 EAS exome AF: 0.992

Gnomad4 SAS exome AF: 0.959

Gnomad4 FIN exome AF: 0.931

Gnomad4 NFE exome AF: 0.982

Gnomad4 OTH exome AF: 0.966

GnomAD4 genome AF: 0.932 AC: 141888 AN: 152208 Hom.: 66416 Cov.: 31 AF XY: 0.931 AC XY: 69289 AN XY: 74422

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.966

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.956

Gnomad4 FIN AF: 0.922

Gnomad4 NFE AF: 0.978

Gnomad4 OTH AF: 0.938

Alfa AF: 0.958 Hom.: 31513

Bravo AF: 0.933

Asia WGS AF: 0.959 AC: 3336 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	-0.91
CADD	Benign	1.7
DANN	Benign	0.35

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: rs6494593; hg19: chr15-32984196;