chr17-67056092-C-T

Variant summary

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

The NM_000727.4(CACNG1):​c.490C>T​(p.Arg164Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000049 in 1,613,254 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 1 hom. )

Consequence

CACNG1
NM_000727.4 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76
Variant links:
Genes affected
CACNG1 (HGNC:1405): (calcium voltage-gated channel auxiliary subunit gamma 1) Voltage-dependent calcium channels are composed of five subunits. The protein encoded by this gene represents one of these subunits, gamma, and is one of two known gamma subunit proteins. This particular gamma subunit is part of skeletal muscle 1,4-dihydropyridine-sensitive calcium channels and is an integral membrane protein that plays a role in excitation-contraction coupling. 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 that function as transmembrane AMPA receptor regulatory proteins (TARPs). [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
CACNG1NM_000727.4 linkc.490C>T p.Arg164Cys missense_variant Exon 4 of 4 ENST00000226021.5 NP_000718.1 Q06432

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNG1ENST00000226021.5 linkc.490C>T p.Arg164Cys missense_variant Exon 4 of 4 1 NM_000727.4 ENSP00000226021.3 Q06432

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151976
Hom.:
0
Cov.:
32
show subpopulations
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:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000876
AC:
22
AN:
251146
Hom.:
0
AF XY:
0.0000958
AC XY:
13
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000621
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000534
AC:
78
AN:
1461278
Hom.:
1
Cov.:
31
AF XY:
0.0000674
AC XY:
49
AN XY:
726950
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151976
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74214
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000139
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.000164
EpiControl
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
Jan 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.490C>T (p.R164C) alteration is located in exon 4 (coding exon 4) of the CACNG1 gene. This alteration results from a C to T substitution at nucleotide position 490, causing the arginine (R) at amino acid position 164 to be replaced by a cysteine (C). 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
0.63
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.11
T
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Uncertain
0.26
D
MetaRNN
Uncertain
0.63
D
MetaSVM
Uncertain
0.018
D
MutationAssessor
Uncertain
2.8
M
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-1.7
N
REVEL
Uncertain
0.62
Sift
Benign
0.082
T
Sift4G
Uncertain
0.012
D
Polyphen
1.0
D
Vest4
0.70
MutPred
0.62
Loss of disorder (P = 0.0055);
MVP
0.84
MPC
1.2
ClinPred
0.35
T
GERP RS
4.8
Varity_R
0.35
gMVP
0.78

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.

Other links and lift over

dbSNP: rs143055819; hg19: chr17-65052208; COSMIC: COSV56826031; API