Variant 19-53982277-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031895.6(CACNG8):c.706T>G(p.Cys236Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,611,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

CACNG8
NM_031895.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

CACNG8 (HGNC:13628): (calcium voltage-gated channel auxiliary subunit gamma 8) 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 and is located in a cluster with two family members, a type II TARP and a calcium channel gamma subunit. The mRNA for this gene is believed to initiate translation from a non-AUG (CUG) start codon. [provided by RefSeq, Dec 2010]

CACNG8 links:

MIR935 (HGNC:):

MIR935 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12116897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNG8	NM_031895.6 linkuse as main transcript	c.706T>G	p.Cys236Gly	missense_variant	4/4	ENST00000270458.4	NP_114101.4	Q8WXS5
MIR935	NR_030632.1 linkuse as main transcript	n.-30T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNG8	ENST00000270458.4 linkuse as main transcript	c.706T>G	p.Cys236Gly	missense_variant	4/4	1	NM_031895.6	ENSP00000270458.3		Q8WXS5A0A1X7SBR8
MIR935	ENST00000401179.1 linkuse as main transcript	n.-30T>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000164

AC:

AN:

244618

Hom.:

AF XY:

0.000180

AC XY:

AN XY:

133528

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000346

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000354

AC:

516

AN:

1459640

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

244

AN XY:

726126

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000449

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000171

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000383

Hom.:

Bravo

AF:

0.000132

ExAC

AF:

0.000116

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000416

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

Feb 23, 2023

The c.706T>G (p.C236G) alteration is located in exon 4 (coding exon 4) of the CACNG8 gene. This alteration results from a T to G substitution at nucleotide position 706, causing the cysteine (C) at amino acid position 236 to be replaced by a glycine (G). 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

Benign

0.27

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Benign

0.94

DEOGEN2

Benign

0.23

.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.55

T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.97

.;L

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-3.0

D;.

REVEL

Benign

0.17

Sift

Uncertain

0.0080

D;.

Sift4G

Benign

0.37

T;.

Polyphen

0.95

.;P

Vest4

0.32

MVP

0.18

ClinPred

0.12

GERP RS

1.8

Varity_R

0.42

gMVP

0.75

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