15-32670039-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144757.3(SCG5):c.227-9727C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,040 control chromosomes in the GnomAD database, including 8,414 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 0.32 (8414 hom., cov: 34)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735

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:):

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCG5	NM_001144757.3	c.227-9727C>T		intron_variant		ENST00000300175.9
ARHGAP11A-SCG5	NM_001368319.1	c.1469-9727C>T		intron_variant
SCG5-AS1	NR_135505.1	n.77-921G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCG5	ENST00000300175.9	c.227-9727C>T		intron_variant		1	NM_001144757.3	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48966 AN: 151922 Hom.: 8395 Cov.: 34

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.322 AC: 49026 AN: 152040 Hom.: 8414 Cov.: 34 AF XY: 0.320 AC XY: 23820 AN XY: 74322

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.313

Alfa AF: 0.345 Hom.: 3767

Bravo AF: 0.320

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.70
Dann	Benign	0.66

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: rs17228571; hg19: chr15-32962240;