15-32666510-C-T

Variant names:

• chr15-32666510-C-T
• rs1406387
• NM_001144757.3:c.227-13256C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144757.3(SCG5):​c.227-13256C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,058 control chromosomes in the GnomAD database, including 15,890 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (15890 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.38
• Publications: 8 publications found

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]

SCG5-AS1 (HGNC:40524): (SCG5 antisense RNA 1)

LOC124903458 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144757.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG5	NM_001144757.3	MANE Select	c.227-13256C>T		intron	N/A	NP_001138229.1	P05408-1
	ARHGAP11A-SCG5	NM_001368319.1		c.1469-13256C>T		intron	N/A	NP_001355248.1	A0A8I5KWH8
	SCG5	NM_003020.5		c.227-13256C>T		intron	N/A	NP_003011.1	P05408-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG5	ENST00000300175.9	TSL:1 MANE Select	c.227-13256C>T		intron	N/A	ENSP00000300175.4	P05408-1
	ARHGAP11A-SCG5	ENST00000692248.1		c.1469-13256C>T		intron	N/A	ENSP00000510771.1	A0A8I5KWH8
	SCG5	ENST00000413748.6	TSL:1	c.227-13256C>T		intron	N/A	ENSP00000388560.2	P05408-2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68497 AN: 151938 Hom.: 15842 Cov.: 33

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.418

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.451 AC: 68609 AN: 152058 Hom.: 15890 Cov.: 33 AF XY: 0.451 AC XY: 33518 AN XY: 74324

African (AFR) AF: 0.546 AC: 22641 AN: 41468

American (AMR) AF: 0.482 AC: 7362 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1177 AN: 3468

East Asian (EAS) AF: 0.442 AC: 2289 AN: 5176

South Asian (SAS) AF: 0.461 AC: 2219 AN: 4816

European-Finnish (FIN) AF: 0.426 AC: 4499 AN: 10556

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27125 AN: 67980

Other (OTH) AF: 0.425 AC: 897 AN: 2110

Alfa AF: 0.412 Hom.: 21862

Bravo AF: 0.460

Asia WGS AF: 0.486 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0020
DANN	Benign	0.61
PhyloP100		-5.4
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

Other links and lift over

dbSNP: rs1406387; hg19: chr15-32958711;