Variant chr15-32680053-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001144757.3(SCG5):c.376+138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 774,472 control chromosomes in the GnomAD database, including 1,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 236 hom., cov: 32)

Exomes 𝑓: 0.055 ( 1231 hom. )

Consequence

SCG5
NM_001144757.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0190

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=-0.87).

BP6

Variant 15-32680053-G-A is Benign according to our data. Variant chr15-32680053-G-A is described in ClinVar as [Benign]. Clinvar id is 1236383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCG5	NM_001144757.3 linkuse as main transcript	c.376+138G>A		intron_variant		ENST00000300175.9	NP_001138229.1
ARHGAP11A-SCG5	NM_001368319.1 linkuse as main transcript	c.1618+138G>A		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.376+138G>A		intron_variant		1	NM_001144757.3	ENSP00000300175	P1	P05408-1

Frequencies

GnomAD3 genomes

AF:

0.0471

AC:

7159

AN:

152122

Hom.:

236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.0499

Gnomad ASJ

AF:

0.0372

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00850

Gnomad FIN

AF:

0.0581

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0698

Gnomad OTH

AF:

0.0479

GnomAD4 exome

AF:

0.0550

AC:

34193

AN:

622232

Hom.:

1231

AF XY:

0.0535

AC XY:

17269

AN XY:

322578

show subpopulations

Gnomad4 AFR exome

AF:

0.0173

Gnomad4 AMR exome

AF:

0.0390

Gnomad4 ASJ exome

AF:

0.0374

Gnomad4 EAS exome

AF:

0.0000882

Gnomad4 SAS exome

AF:

0.00718

Gnomad4 FIN exome

AF:

0.0523

Gnomad4 NFE exome

AF:

0.0680

Gnomad4 OTH exome

AF:

0.0522

GnomAD4 genome

AF:

0.0470

AC:

7159

AN:

152240

Hom.:

236

Cov.:

AF XY:

0.0453

AC XY:

3371

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0179

Gnomad4 AMR

AF:

0.0498

Gnomad4 ASJ

AF:

0.0372

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00871

Gnomad4 FIN

AF:

0.0581

Gnomad4 NFE

AF:

0.0698

Gnomad4 OTH

AF:

0.0474

Alfa

AF:

0.0569

Hom.:

Bravo

AF:

0.0457

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.9

DANN

Benign

0.62

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