Variant chr15-32692014-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001144757.3(SCG5):c.543+251C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,364,774 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 5 hom. )

Consequence

SCG5
NM_001144757.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.443

Variant links:

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]

SCG5 links:

ARHGAP11A-SCG5 (HGNC:):

ARHGAP11A-SCG5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 15-32692014-C-T is Benign according to our data. Variant chr15-32692014-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000651 (789/1212494) while in subpopulation AFR AF= 0.0166 (438/26356). AF 95% confidence interval is 0.0153. There are 5 homozygotes in gnomad4_exome. There are 351 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCG5	NM_001144757.3 linkuse as main transcript	c.543+251C>T		intron_variant		ENST00000300175.9	NP_001138229.1
ARHGAP11A-SCG5	NM_001368319.1 linkuse as main transcript	c.1782+251C>T		intron_variant			NP_001355248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9 linkuse as main transcript	c.543+251C>T		intron_variant		1	NM_001144757.3	ENSP00000300175	P1	P05408-1

Frequencies

GnomAD3 genomes

AF:

0.00432

AC:

658

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00478

GnomAD4 exome

AF:

0.000651

AC:

789

AN:

1212494

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

351

AN XY:

581500

show subpopulations

Gnomad4 AFR exome

AF:

0.0166

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.000114

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000216

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000239

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00441

AC:

671

AN:

152280

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

293

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00275

Hom.:

Bravo

AF:

0.00469

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.7

DANN

Benign

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over