rs12442397

Variant names:

• chr15-32680738-T-A
• rs12442397
• NM_001144757.3:c.376+823T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-32680738-T-A
• chr15-32680738-T-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.376+823T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,828 control chromosomes in the GnomAD database, including 25,653 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 0.56 (25653 hom., cov: 30)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.376+823T>A		intron_variant	Intron 3 of 5	ENST00000300175.9	NP_001138229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.376+823T>A		intron_variant	Intron 3 of 5	1	NM_001144757.3	ENSP00000300175.4
ARHGAP11A-SCG5	ENST00000692248.1	c.1618+823T>A		intron_variant	Intron 11 of 13			ENSP00000510771.1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85673 AN: 151708 Hom.: 25645 Cov.: 30

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.564 AC: 85700 AN: 151828 Hom.: 25653 Cov.: 30 AF XY: 0.555 AC XY: 41212 AN XY: 74194

African (AFR) AF: 0.386 AC: 15955 AN: 41376

American (AMR) AF: 0.612 AC: 9329 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2556 AN: 3470

East Asian (EAS) AF: 0.339 AC: 1739 AN: 5136

South Asian (SAS) AF: 0.505 AC: 2432 AN: 4818

European-Finnish (FIN) AF: 0.496 AC: 5223 AN: 10522

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46340 AN: 67944

Other (OTH) AF: 0.582 AC: 1229 AN: 2112

Alfa AF: 0.608 Hom.: 3483

Bravo AF: 0.570

Asia WGS AF: 0.409 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.52
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12442397; hg19: chr15-32972939;