Variant 17-66884565-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_145811.3(CACNG5):c.474T>G(p.Asp158Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CACNG5
NM_145811.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.77

Variant links:

Genes affected

CACNG5 (HGNC:1409): (calcium voltage-gated channel auxiliary subunit gamma 5) The protein encoded by this gene is a type II transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family and is located in a cluster with two family members, a type I TARP and a calcium channel gamma subunit. This gene is a susceptibility locus for schizophrenia and bipolar disorder. [provided by RefSeq, Dec 2010]

CACNG5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNG5	NM_145811.3 linkuse as main transcript	c.474T>G	p.Asp158Glu	missense_variant	5/6	ENST00000533854.6
CACNG5	NM_001371476.1 linkuse as main transcript	c.424+3868T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CACNG5	ENST00000533854.6 linkuse as main transcript	c.474T>G	p.Asp158Glu	missense_variant	5/6	2	NM_145811.3	P1
CACNG5	ENST00000307139.4 linkuse as main transcript	c.474T>G	p.Asp158Glu	missense_variant	4/5	1		P1
CACNG5	ENST00000673855.1 linkuse as main transcript	c.424+3868T>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152002

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000281

AC:

408

AN:

1451098

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

188

AN XY:

722280

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000330

Gnomad4 OTH exome

AF:

0.000316

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

152002

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74246

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.474T>G (p.D158E) alteration is located in exon 4 (coding exon 4) of the CACNG5 gene. This alteration results from a T to G substitution at nucleotide position 474, causing the aspartic acid (D) at amino acid position 158 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

0.0096

BayesDel_noAF

Benign

-0.22

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.15

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Uncertain

-0.084

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-2.2

N;N

REVEL

Uncertain

0.49

Sift

Benign

0.040

D;D

Sift4G

Benign

0.061

T;T

Polyphen

0.97

D;D

Vest4

0.84

MutPred

0.37

Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);

MVP

0.62

MPC

0.75

ClinPred

0.89

GERP RS

-4.2

Varity_R

0.18

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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