chr15-32679733-C-T

Variant names:

• chr15-32679733-C-T
• rs7177843
• NM_001144757.3:c.227-33C>T

Variant summary

Our verdict is Benign. The variant received -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:56310): (ARHGAP11A-SCG5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ARHGAP11A (Rho GTPase activating protein 11A) and SCG5 (secretogranin V) genes on chromosome 15q13.3. The readthrough transcript encodes a fusion protein that shares sequence identity with both the ARHGAP11A and SCG5 gene products. [provided by RefSeq, Feb 2019]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.227-33C>T		intron_variant	Intron 2 of 5	ENST00000300175.9	NP_001138229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.227-33C>T		intron_variant	Intron 2 of 5	1	NM_001144757.3	ENSP00000300175.4
ARHGAP11A-SCG5	ENST00000692248.1	c.1469-33C>T		intron_variant	Intron 10 of 13			ENSP00000510771.1

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

GnomAD2 exomes AF: 0.299 AC: 74352 AN: 248296 AF XY: 0.301

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 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 AC: 7131 AN: 33374

Gnomad4 AMR exome AF: 0.312 AC: 13944 AN: 44672

Gnomad4 ASJ exome AF: 0.191 AC: 4980 AN: 26048

Gnomad4 EAS exome AF: 0.589 AC: 23360 AN: 39646

Gnomad4 SAS exome AF: 0.403 AC: 34667 AN: 85976

Gnomad4 FIN exome AF: 0.369 AC: 19683 AN: 53374

Gnomad4 NFE exome AF: 0.218 AC: 241265 AN: 1105686

Gnomad4 Remaining exome AF: 0.267 AC: 16037 AN: 60114

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 AC: 0.218666 AN: 0.218666

Gnomad4 AMR AF: 0.282 AC: 0.281721 AN: 0.281721

Gnomad4 ASJ AF: 0.189 AC: 0.188761 AN: 0.188761

Gnomad4 EAS AF: 0.592 AC: 0.59207 AN: 0.59207

Gnomad4 SAS AF: 0.421 AC: 0.421337 AN: 0.421337

Gnomad4 FIN AF: 0.366 AC: 0.366212 AN: 0.366212

Gnomad4 NFE AF: 0.225 AC: 0.225102 AN: 0.225102

Gnomad4 OTH AF: 0.260 AC: 0.260436 AN: 0.260436

Alfa AF: 0.233 Hom.: 16874

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.3
DANN	Benign	0.73
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV107356599; COSMIC: COSV107356599;