Genetic Variant CACNG3:p.Pro307Pro (chr16-24361836-G-A) – ACMG Classification: Benign (-13 pts)

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

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]

CACNG3 links:

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
CACNG3	NM_006539.4 link	c.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
CACNG3	ENST00000005284.4 link	c.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.:

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.:

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:

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

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

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.:

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0432

AC:

2937

AN:

68008

Other (OTH)

AF:

0.0346

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

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

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.:

Bravo

AF:

0.0286

Asia WGS

AF:

0.0210

AC:

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

(source)

DANN

Benign

0.67

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over