rs375730739

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145814.2(CACNG6):c.262A>G(p.Thr88Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,548,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. T88I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

CACNG6
NM_145814.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0200

Publications

0 publications found

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]

CACNG6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017474025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145814.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CACNG6	NM_145814.2	MANE Select	c.262A>G	p.Thr88Ala	missense	Exon 1 of 4	NP_665813.1	Q9BXT2
CACNG6	NM_145815.2		c.262A>G	p.Thr88Ala	missense	Exon 1 of 3	NP_665814.1	A6NFR2
CACNG6	NM_031897.3		c.262A>G	p.Thr88Ala	missense	Exon 1 of 2	NP_114103.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CACNG6	ENST00000252729.7	TSL:1 MANE Select	c.262A>G	p.Thr88Ala	missense	Exon 1 of 4	ENSP00000252729.2	Q9BXT2
CACNG6	ENST00000955412.1		c.262A>G	p.Thr88Ala	missense	Exon 1 of 3	ENSP00000625471.1
CACNG6	ENST00000346968.2	TSL:5	c.262A>G	p.Thr88Ala	missense	Exon 1 of 3	ENSP00000319097.2	A6NFR2

Frequencies

GnomAD3 genomes

AF:

0.000743

AC:

113

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

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:

0.000956

GnomAD2 exomes

AF:

0.000150

AC:

AN:

140264

AF XY:

0.000133

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.0000820

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000243

GnomAD4 exome

AF:

0.0000544

AC:

AN:

1395898

Hom.:

Cov.:

AF XY:

0.0000465

AC XY:

AN XY:

688650

show subpopulations

African (AFR)

AF:

0.00203

AC:

AN:

31526

American (AMR)

AF:

0.000112

AC:

AN:

35648

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25084

East Asian (EAS)

AF:

0.00

AC:

AN:

35692

South Asian (SAS)

AF:

0.00

AC:

AN:

79170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078148

Other (OTH)

AF:

0.000138

AC:

AN:

57906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000736

AC:

112

AN:

152256

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00236

AC:

AN:

41550

American (AMR)

AF:

0.000785

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000260

Hom.:

Bravo

AF:

0.000767

ESP6500AA

AF:

0.00132

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000703

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.098

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.58

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

PhyloP100

-0.020

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.6

REVEL

Benign

0.030

Sift

Benign

0.080

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.028

MVP

0.65

MPC

0.47

ClinPred

0.0071

GERP RS

1.5

PromoterAI

-0.0043

Neutral

(source)

Varity_R

0.071

gMVP

0.46

Mutation Taster

=96/4

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over