17-66885029-C-T

Variant names:

• chr17-66885029-C-T
• rs149774604
• NM_145811.3:c.617C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_145811.3(CACNG5):​c.617C>T​(p.Ala206Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,614,150 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A206E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0023 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: CACNG5 NM_145811.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005459398).
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.617C>T	p.Ala206Val	missense	Exon 6 of 6	NP_665810.1	Q9UF02
	CACNG5	NM_001371476.1		c.424+4332C>T		intron	N/A	NP_001358405.1	A0A669KBF6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG5	ENST00000533854.6	TSL:2 MANE Select	c.617C>T	p.Ala206Val	missense	Exon 6 of 6	ENSP00000436836.1	Q9UF02
	CACNG5	ENST00000307139.4	TSL:1	c.617C>T	p.Ala206Val	missense	Exon 5 of 5	ENSP00000303092.3	Q9UF02
	CACNG5	ENST00000673855.1		c.424+4332C>T		intron	N/A	ENSP00000501267.1	A0A669KBF6

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 343 AN: 152156 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00799

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

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: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000660 AC: 166 AN: 251378 AF XY: 0.000508

Gnomad AFR exome AF: 0.00905

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000233 AC: 340 AN: 1461876 Hom.: 0 Cov.: 33 AF XY: 0.000221 AC XY: 161 AN XY: 727240

African (AFR) AF: 0.00809 AC: 271 AN: 33480

American (AMR) AF: 0.000425 AC: 19 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111994

Other (OTH) AF: 0.000364 AC: 22 AN: 60396

GnomAD4 genome AF: 0.00226 AC: 344 AN: 152274 Hom.: 3 Cov.: 33 AF XY: 0.00208 AC XY: 155 AN XY: 74460

African (AFR) AF: 0.00799 AC: 332 AN: 41550

American (AMR) AF: 0.000392 AC: 6 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68018

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000622 Hom.: 0

Bravo AF: 0.00266

ESP6500AA AF: 0.00885 AC: 39

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000815 AC: 99

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
Eigen	Benign	0.057
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.8
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Benign	0.090	T
Sift4G	Benign	0.17	T
Polyphen		0.98	D
Vest4		0.49
MVP		0.25
MPC		0.42
ClinPred		0.017	T
GERP RS		3.4
Varity_R		0.068
gMVP		0.42
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs149774604; hg19: chr17-64881146;