Variant rs200135028 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001144757.3(SCG5):c.482G>A(p.Gly161Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCG5
NM_001144757.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.93

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3126297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCG5	NM_001144757.3 link	c.482G>A	p.Gly161Asp	missense_variant	Exon 4 of 6	ENST00000300175.9	NP_001138229.1	P05408-1A0A024R9I1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9 link	c.482G>A	p.Gly161Asp	missense_variant	Exon 4 of 6	1	NM_001144757.3	ENSP00000300175.4		P05408-1
ARHGAP11A-SCG5	ENST00000692248.1 link	c.1721G>A	p.Gly574Asp	missense_variant	Exon 12 of 14			ENSP00000510771.1		A0A8I5KWH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247582

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457798

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725312

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;.;T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.0025

MetaRNN

Benign

0.31

T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.6

L;.;.;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.45

N;N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.13

T;T;D;D;D

Sift4G

Benign

0.18

T;T;T;T;D

Polyphen

0.67

P;.;.;.;.

Vest4

0.48

MutPred

0.41

Gain of ubiquitination at K166 (P = 0.0388);.;.;Gain of ubiquitination at K166 (P = 0.0388);.;

MVP

0.58

MPC

0.28

ClinPred

0.54

GERP RS

5.7

Varity_R

0.14

gMVP

0.47

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over