NM_001144757.3:c.489+2853A>T

Variant names:

• chr15-32687522-A-T
• rs11638903
• NM_001144757.3:c.489+2853A>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.489+2853A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,100 control chromosomes in the GnomAD database, including 5,841 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 0.27 (5841 hom., cov: 32)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 4 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]

ENSG00000298771 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.489+2853A>T		intron_variant	Intron 4 of 5	ENST00000300175.9	NP_001138229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.489+2853A>T		intron_variant	Intron 4 of 5	1	NM_001144757.3	ENSP00000300175.4
ARHGAP11A-SCG5	ENST00000692248.1	c.1728+2853A>T		intron_variant	Intron 12 of 13			ENSP00000510771.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41081 AN: 151982 Hom.: 5833 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.270 AC: 41096 AN: 152100 Hom.: 5841 Cov.: 32 AF XY: 0.270 AC XY: 20067 AN XY: 74332

African (AFR) AF: 0.177 AC: 7330 AN: 41506

American (AMR) AF: 0.332 AC: 5079 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1090 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1576 AN: 5168

South Asian (SAS) AF: 0.303 AC: 1462 AN: 4824

European-Finnish (FIN) AF: 0.257 AC: 2717 AN: 10560

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20795 AN: 67974

Other (OTH) AF: 0.274 AC: 578 AN: 2110

Alfa AF: 0.172 Hom.: 378

Bravo AF: 0.273

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.59
PhyloP100		2.1
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: rs11638903; hg19: chr15-32979723;