16-24361836-G-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006539.4(CACNG3):​c.921G>A​(p.Pro307Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 1,610,680 control chromosomes in the GnomAD database, including 1,504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.033 ( 117 hom., cov: 31)
Exomes 𝑓: 0.041 ( 1387 hom. )

Consequence

CACNG3
NM_006539.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.216

Publications

7 publications found
Variant links:
Genes affected
CACNG3 (HGNC:1407): (calcium voltage-gated channel auxiliary subunit gamma 3) The protein encoded by this gene is a type I 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. This gene is a susceptibility locus for childhood absence epilepsy. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP7
Synonymous conserved (PhyloP=-0.216 with no splicing effect.
BA1
GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0566 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNG3NM_006539.4 linkc.921G>A p.Pro307Pro synonymous_variant Exon 4 of 4 ENST00000005284.4 NP_006530.1 O60359

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNG3ENST00000005284.4 linkc.921G>A p.Pro307Pro synonymous_variant Exon 4 of 4 1 NM_006539.4 ENSP00000005284.4 O60359

Frequencies

GnomAD3 genomes
AF:
0.0333
AC:
5066
AN:
152032
Hom.:
117
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0158
Gnomad AMI
AF:
0.00877
Gnomad AMR
AF:
0.0210
Gnomad ASJ
AF:
0.0320
Gnomad EAS
AF:
0.000771
Gnomad SAS
AF:
0.0458
Gnomad FIN
AF:
0.0678
Gnomad MID
AF:
0.0601
Gnomad NFE
AF:
0.0432
Gnomad OTH
AF:
0.0345
GnomAD2 exomes
AF:
0.0374
AC:
9275
AN:
247904
AF XY:
0.0399
show subpopulations
Gnomad AFR exome
AF:
0.0150
Gnomad AMR exome
AF:
0.0162
Gnomad ASJ exome
AF:
0.0233
Gnomad EAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.0684
Gnomad NFE exome
AF:
0.0436
Gnomad OTH exome
AF:
0.0366
GnomAD4 exome
AF:
0.0410
AC:
59822
AN:
1458530
Hom.:
1387
Cov.:
32
AF XY:
0.0418
AC XY:
30321
AN XY:
725604
show subpopulations
African (AFR)
AF:
0.0149
AC:
500
AN:
33476
American (AMR)
AF:
0.0169
AC:
757
AN:
44704
Ashkenazi Jewish (ASJ)
AF:
0.0237
AC:
617
AN:
26088
East Asian (EAS)
AF:
0.000252
AC:
10
AN:
39686
South Asian (SAS)
AF:
0.0579
AC:
4993
AN:
86206
European-Finnish (FIN)
AF:
0.0677
AC:
3425
AN:
50588
Middle Eastern (MID)
AF:
0.0501
AC:
289
AN:
5764
European-Non Finnish (NFE)
AF:
0.0423
AC:
47039
AN:
1111646
Other (OTH)
AF:
0.0363
AC:
2192
AN:
60372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
3012
6025
9037
12050
15062
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1732
3464
5196
6928
8660
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0333
AC:
5070
AN:
152150
Hom.:
117
Cov.:
31
AF XY:
0.0334
AC XY:
2485
AN XY:
74370
show subpopulations
African (AFR)
AF:
0.0158
AC:
657
AN:
41520
American (AMR)
AF:
0.0210
AC:
320
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
0.0320
AC:
111
AN:
3466
East Asian (EAS)
AF:
0.000773
AC:
4
AN:
5176
South Asian (SAS)
AF:
0.0461
AC:
221
AN:
4796
European-Finnish (FIN)
AF:
0.0678
AC:
719
AN:
10598
Middle Eastern (MID)
AF:
0.0680
AC:
20
AN:
294
European-Non Finnish (NFE)
AF:
0.0432
AC:
2937
AN:
68008
Other (OTH)
AF:
0.0346
AC:
73
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
253
505
758
1010
1263
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
70
140
210
280
350
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0311
Hom.:
72
Bravo
AF:
0.0286
Asia WGS
AF:
0.0210
AC:
74
AN:
3478
EpiCase
AF:
0.0436
EpiControl
AF:
0.0443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
9.2
DANN
Benign
0.67
PhyloP100
-0.22
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12928078; hg19: chr16-24373157; COSMIC: COSV50066389; API