19-53992885-G-C

Variant summary

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

The NM_145814.2(CACNG6):ā€‹c.8G>Cā€‹(p.Trp3Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000047 in 1,403,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000052 ( 0 hom. )

Consequence

CACNG6
NM_145814.2 missense

Scores

7
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.27
Variant links:
Genes affected
CACNG6 (HGNC:13625): (calcium voltage-gated channel auxiliary subunit gamma 6) 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 an integral membrane protein that is thought to stabilize the calcium channel in an inactive (closed) state. 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). Alternative splicing results in multiple transcript variants. Variants in this gene have been associated with aspirin-intolerant asthma. [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/exons MANE UniProt
CACNG6NM_145814.2 linkuse as main transcriptc.8G>C p.Trp3Ser missense_variant 1/4 ENST00000252729.7
CACNG6NM_145815.2 linkuse as main transcriptc.8G>C p.Trp3Ser missense_variant 1/3
CACNG6NM_031897.3 linkuse as main transcriptc.8G>C p.Trp3Ser missense_variant 1/2
CACNG6NR_102308.2 linkuse as main transcriptn.49+1688G>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNG6ENST00000252729.7 linkuse as main transcriptc.8G>C p.Trp3Ser missense_variant 1/41 NM_145814.2 P1
CACNG6ENST00000346968.2 linkuse as main transcriptc.8G>C p.Trp3Ser missense_variant 1/35
CACNG6ENST00000352529.1 linkuse as main transcriptc.8G>C p.Trp3Ser missense_variant 1/25

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152156
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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
GnomAD3 exomes
AF:
0.00000920
AC:
1
AN:
108722
Hom.:
0
AF XY:
0.0000166
AC XY:
1
AN XY:
60288
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000520
AC:
65
AN:
1250776
Hom.:
0
Cov.:
31
AF XY:
0.0000442
AC XY:
27
AN XY:
610478
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000223
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:
0.0000602
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152268
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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
Bravo
AF:
0.00000378
ExAC
AF:
0.00000893
AC:
1

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 submitterclinical testingAmbry GeneticsJun 10, 2022The c.8G>C (p.W3S) alteration is located in exon 1 (coding exon 1) of the CACNG6 gene. This alteration results from a G to C substitution at nucleotide position 8, causing the tryptophan (W) at amino acid position 3 to be replaced by a serine (S). 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
0.83
BayesDel_addAF
Uncertain
0.058
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.48
.;T;.
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.76
T;T;T
M_CAP
Pathogenic
0.30
D
MetaRNN
Uncertain
0.67
D;D;D
MetaSVM
Benign
-0.73
T
MutationAssessor
Uncertain
2.3
.;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-5.9
D;D;D
REVEL
Uncertain
0.38
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.56
MutPred
0.38
Loss of MoRF binding (P = 0.0084);Loss of MoRF binding (P = 0.0084);Loss of MoRF binding (P = 0.0084);
MVP
0.77
MPC
1.8
ClinPred
0.99
D
GERP RS
3.1
Varity_R
0.91
gMVP
0.68

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: rs771562119; hg19: chr19-54496139; API