Variant 17-66878981-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145811.3(CACNG5):c.206G>C(p.Arg69Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,460,260 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CACNG5
NM_145811.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNG5	NM_145811.3 linkuse as main transcript	c.206G>C	p.Arg69Pro	missense_variant	3/6	ENST00000533854.6	NP_665810.1
CACNG5	NM_001371476.1 linkuse as main transcript	c.206G>C	p.Arg69Pro	missense_variant	3/5		NP_001358405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CACNG5	ENST00000533854.6 linkuse as main transcript	c.206G>C	p.Arg69Pro	missense_variant	3/6	2	NM_145811.3	ENSP00000436836	P1
CACNG5	ENST00000307139.4 linkuse as main transcript	c.206G>C	p.Arg69Pro	missense_variant	2/5	1		ENSP00000303092	P1
CACNG5	ENST00000673855.1 linkuse as main transcript	c.206G>C	p.Arg69Pro	missense_variant	2/4			ENSP00000501267

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250756

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135508

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1460260

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726484

show subpopulations

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:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000327

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

Mar 27, 2023

The c.206G>C (p.R69P) alteration is located in exon 2 (coding exon 2) of the CACNG5 gene. This alteration results from a G to C substitution at nucleotide position 206, causing the arginine (R) at amino acid position 69 to be replaced by a proline (P). 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

Benign

0.19

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

D;D

Eigen

Benign

-0.079

Eigen_PC

Benign

0.028

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

.;D

M_CAP

Benign

0.075

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Uncertain

-0.059

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-4.1

D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.027

D;D

Polyphen

0.10

B;B

Vest4

0.74

MutPred

0.48

Loss of methylation at R69 (P = 0.0256);Loss of methylation at R69 (P = 0.0256);

MVP

0.76

MPC

0.32

ClinPred

0.39

GERP RS

3.6

Varity_R

0.70

gMVP

0.80

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