chr17-66878980-C-T

Variant summary

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

The NM_145811.3(CACNG5):​c.205C>T​(p.Arg69Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000868 in 1,612,576 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000088 ( 1 hom. )

Consequence

CACNG5
NM_145811.3 missense

Scores

2
13
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24
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]

Genome browser will be placed here

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 rank MANE Protein UniProt
CACNG5NM_145811.3 linkc.205C>T p.Arg69Trp missense_variant Exon 3 of 6 ENST00000533854.6 NP_665810.1 Q9UF02
CACNG5NM_001371476.1 linkc.205C>T p.Arg69Trp missense_variant Exon 3 of 5 NP_001358405.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNG5ENST00000533854.6 linkc.205C>T p.Arg69Trp missense_variant Exon 3 of 6 2 NM_145811.3 ENSP00000436836.1 Q9UF02
CACNG5ENST00000307139.4 linkc.205C>T p.Arg69Trp missense_variant Exon 2 of 5 1 ENSP00000303092.3 Q9UF02
CACNG5ENST00000673855.1 linkc.205C>T p.Arg69Trp missense_variant Exon 2 of 4 ENSP00000501267.1 A0A669KBF6

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
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:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
250760
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135516
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000883
AC:
129
AN:
1460252
Hom.:
1
Cov.:
30
AF XY:
0.0000743
AC XY:
54
AN XY:
726490
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.000114
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000722
AC:
11
AN:
152324
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0000481
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:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.205C>T (p.R69W) alteration is located in exon 2 (coding exon 2) of the CACNG5 gene. This alteration results from a C to T substitution at nucleotide position 205, causing the arginine (R) at amino acid position 69 to be replaced by a tryptophan (W). 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
0.11
BayesDel_addAF
Benign
-0.070
T
BayesDel_noAF
Uncertain
-0.060
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.75
D;D
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.97
.;D
M_CAP
Benign
0.084
D
MetaRNN
Uncertain
0.61
D;D
MetaSVM
Uncertain
0.30
D
MutationAssessor
Uncertain
2.0
M;M
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-5.4
D;D
REVEL
Uncertain
0.55
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
0.91
P;P
Vest4
0.59
MVP
0.87
MPC
0.49
ClinPred
0.61
D
GERP RS
4.5
Varity_R
0.48
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs201854089; hg19: chr17-64875098; COSMIC: COSV50055561; API