rs12595007

Variant names:

• chr15-32642887-C-G
• rs12595007
• NM_001144757.3:c.-7-699C>G

Variant summary

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

The NM_001144757.3(SCG5):​c.-7-699C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,136 control chromosomes in the GnomAD database, including 1,454 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 0.13 (1454 hom., cov: 31)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.-7-699C>G		intron_variant	Intron 1 of 5	ENST00000300175.9	NP_001138229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.-7-699C>G		intron_variant	Intron 1 of 5	1	NM_001144757.3	ENSP00000300175.4
ARHGAP11A-SCG5	ENST00000692248.1	c.1236-699C>G		intron_variant	Intron 9 of 13			ENSP00000510771.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19842 AN: 152018 Hom.: 1454 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0211

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0612

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.131 AC: 19862 AN: 152136 Hom.: 1454 Cov.: 31 AF XY: 0.125 AC XY: 9293 AN XY: 74386

African (AFR) AF: 0.125 AC: 5198 AN: 41480

American (AMR) AF: 0.114 AC: 1738 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3468

East Asian (EAS) AF: 0.0212 AC: 110 AN: 5192

South Asian (SAS) AF: 0.116 AC: 557 AN: 4816

European-Finnish (FIN) AF: 0.0612 AC: 649 AN: 10598

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10571 AN: 67982

Other (OTH) AF: 0.138 AC: 292 AN: 2112

Alfa AF: 0.143 Hom.: 191

Bravo AF: 0.133

Asia WGS AF: 0.0750 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.44
PhyloP100		-1.5
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: rs12595007; hg19: chr15-32935088;