Genetic Variant CACNG5:p.Asp158Glu (chr17-66884565-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145811.3(CACNG5):c.474T>A(p.Asp158Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,838 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 1 hom. )

Consequence

CACNG5
NM_145811.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.77

Publications

0 publications found

Variant links:

Genes affected

CACNG5 (HGNC:1409): (calcium voltage-gated channel auxiliary subunit gamma 5) The protein encoded by this gene is a type II 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 I TARP and a calcium channel gamma subunit. This gene is a susceptibility locus for schizophrenia and bipolar disorder. [provided by RefSeq, Dec 2010]

CACNG5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145811.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG5	NM_145811.3	MANE Select	c.474T>A	p.Asp158Glu	missense	Exon 5 of 6	NP_665810.1	Q9UF02
	CACNG5	NM_001371476.1		c.424+3868T>A		intron	N/A	NP_001358405.1	A0A669KBF6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CACNG5	ENST00000533854.6	TSL:2 MANE Select	c.474T>A	p.Asp158Glu	missense	Exon 5 of 6	ENSP00000436836.1	Q9UF02
CACNG5	ENST00000307139.4	TSL:1	c.474T>A	p.Asp158Glu	missense	Exon 4 of 5	ENSP00000303092.3	Q9UF02
CACNG5	ENST00000673855.1		c.424+3868T>A		intron	N/A	ENSP00000501267.1	A0A669KBF6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251292

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454838

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

723978

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33358

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1105724

Other (OTH)

AF:

0.00

AC:

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.72

MetaSVM

Uncertain

-0.084

MutationAssessor

Benign

1.9

PhyloP100

-2.8

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.49

Sift

Benign

0.040

Sift4G

Benign

0.061

Polyphen

0.97

Vest4

0.84

MutPred

0.37

Gain of sheet (P = 0.0149)

MVP

0.62

MPC

0.75

ClinPred

0.79

GERP RS

-4.2

Varity_R

0.18

gMVP

0.78

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over