NM_001144757.3:c.543+8G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001144757.3(SCG5):c.543+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,612,164 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 12 hom. )

Consequence

SCG5
NM_001144757.3 splice_region, intron

Scores

Splicing: ADA: 0.0003765

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.282

Publications

0 publications found

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: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]

ARHGAP11A-SCG5 links:

ENSG00000298771 (HGNC:):

ENSG00000298771 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003652513).

BP6

Variant 15-32691771-G-A is Benign according to our data. Variant chr15-32691771-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1701250.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 12 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144757.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCG5	NM_001144757.3	MANE Select	c.543+8G>A	splice_region intron	N/A	NP_001138229.1	P05408-1
ARHGAP11A-SCG5	NM_001368319.1		c.1782+8G>A	splice_region intron	N/A	NP_001355248.1	A0A8I5KWH8
SCG5	NM_003020.5		c.540+8G>A	splice_region intron	N/A	NP_003011.1	P05408-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCG5	ENST00000300175.9	TSL:1 MANE Select	c.543+8G>A	splice_region intron	N/A	ENSP00000300175.4	P05408-1
ARHGAP11A-SCG5	ENST00000692248.1		c.1782+8G>A	splice_region intron	N/A	ENSP00000510771.1	A0A8I5KWH8
SCG5	ENST00000413748.6	TSL:1	c.540+8G>A	splice_region intron	N/A	ENSP00000388560.2	P05408-2

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

157

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00995

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00167

AC:

410

AN:

245824

AF XY:

0.00201

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000706

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000887

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.00112

AC:

1634

AN:

1459910

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

998

AN XY:

726000

show subpopulations

African (AFR)

AF:

0.0000897

AC:

AN:

33442

American (AMR)

AF:

0.000854

AC:

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.0000767

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.00962

AC:

824

AN:

85650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53340

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000572

AC:

636

AN:

1111154

Other (OTH)

AF:

0.00156

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

167

250

334

417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00102

AC:

156

AN:

152254

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41544

American (AMR)

AF:

0.00209

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00995

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000970

AC:

AN:

68012

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000754

Hom.:

Bravo

AF:

0.000880

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00144

AC:

ExAC

AF:

0.00193

AC:

233

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.8

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0092

Eigen

Benign

0.099

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.0096

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

PhyloP100

-0.28

PROVEAN

Benign

0.69

REVEL

Benign

0.14

Sift

Benign

0.087

Sift4G

Benign

0.18

MVP

0.34

ClinPred

0.0078

GERP RS

-0.35

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00038

dbscSNV1_RF

Benign

0.028

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over