Genetic Variant CACNG6:p.Phe6Ser (chr19-53992894-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_145814.2(CACNG6):c.17T>C(p.Phe6Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CACNG6
NM_145814.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35998717).

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.17T>C	p.Phe6Ser	missense	Exon 1 of 4	NP_665813.1	Q9BXT2
CACNG6	NM_145815.2		c.17T>C	p.Phe6Ser	missense	Exon 1 of 3	NP_665814.1	A6NFR2
CACNG6	NM_031897.3		c.17T>C	p.Phe6Ser	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.17T>C	p.Phe6Ser	missense	Exon 1 of 4	ENSP00000252729.2	Q9BXT2
CACNG6	ENST00000955412.1		c.17T>C	p.Phe6Ser	missense	Exon 1 of 3	ENSP00000625471.1
CACNG6	ENST00000346968.2	TSL:5	c.17T>C	p.Phe6Ser	missense	Exon 1 of 3	ENSP00000319097.2	A6NFR2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1252766

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

611826

African (AFR)

AF:

0.00

AC:

AN:

25304

American (AMR)

AF:

0.00

AC:

AN:

18022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16764

East Asian (EAS)

AF:

0.00

AC:

AN:

31070

South Asian (SAS)

AF:

0.00

AC:

AN:

47352

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4930

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1013528

Other (OTH)

AF:

0.00

AC:

AN:

50860

GnomAD4 genome

Cov.:

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

Pathogenic

0.84

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

PhyloP100

4.0

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.25

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.34

MutPred

0.28

Gain of helix (P = 0.0325)

MVP

0.56

MPC

1.9

ClinPred

0.99

GERP RS

3.1

PromoterAI

0.025

Neutral

(source)

Varity_R

0.71

gMVP

0.62

Mutation Taster

=55/45

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over