Variant chr19-53993190-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_145814.2(CACNG6):c.313C>T(p.Pro105Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,389,414 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CACNG6
NM_145814.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

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 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	Protein
CACNG6	NM_145814.2 linkuse as main transcript	c.313C>T	p.Pro105Ser	missense_variant	1/4	ENST00000252729.7	NP_665813.1
CACNG6	NM_145815.2 linkuse as main transcript	c.313C>T	p.Pro105Ser	missense_variant	1/3		NP_665814.1
CACNG6	NM_031897.3 linkuse as main transcript	c.313C>T	p.Pro105Ser	missense_variant	1/2		NP_114103.2
CACNG6	NR_102308.2 linkuse as main transcript	n.49+1993C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CACNG6	ENST00000252729.7 linkuse as main transcript	c.313C>T	p.Pro105Ser	missense_variant	1/4	1	NM_145814.2	ENSP00000252729	P1
CACNG6	ENST00000346968.2 linkuse as main transcript	c.313C>T	p.Pro105Ser	missense_variant	1/3	5		ENSP00000319097
CACNG6	ENST00000352529.1 linkuse as main transcript	c.313C>T	p.Pro105Ser	missense_variant	1/2	5		ENSP00000319135

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000152

AC:

AN:

131370

Hom.:

AF XY:

0.0000139

AC XY:

AN XY:

71714

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000192

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1389414

Hom.:

Cov.:

AF XY:

0.00000292

AC XY:

AN XY:

685572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000561

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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 submitter

clinical testing

Ambry Genetics

Mar 26, 2024

The c.313C>T (p.P105S) alteration is located in exon 1 (coding exon 1) of the CACNG6 gene. This alteration results from a C to T substitution at nucleotide position 313, causing the proline (P) at amino acid position 105 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

0.85

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;T;.

Eigen

Benign

0.18

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Pathogenic

0.46

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.6

.;M;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.0

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.013

D;D;D

Sift4G

Uncertain

0.028

D;D;D

Polyphen

1.0

D;B;B

Vest4

0.59

MutPred

0.41

Loss of glycosylation at T102 (P = 0.0462);Loss of glycosylation at T102 (P = 0.0462);Loss of glycosylation at T102 (P = 0.0462);

MVP

0.84

MPC

0.60

ClinPred

0.94

GERP RS

2.5

Varity_R

0.36

gMVP

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over