rs1434492187

Variant names:

• chr19-53992915-G-A
• rs1434492187
• NM_145814.2:c.38G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145814.2(CACNG6):​c.38G>A​(p.Arg13Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000008 in 1,250,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: CACNG6 NM_145814.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14647737).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG6	NM_145814.2	MANE Select	c.38G>A	p.Arg13Gln	missense	Exon 1 of 4	NP_665813.1	Q9BXT2
	CACNG6	NM_145815.2		c.38G>A	p.Arg13Gln	missense	Exon 1 of 3	NP_665814.1	A6NFR2
	CACNG6	NM_031897.3		c.38G>A	p.Arg13Gln	missense	Exon 1 of 2	NP_114103.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG6	ENST00000252729.7	TSL:1 MANE Select	c.38G>A	p.Arg13Gln	missense	Exon 1 of 4	ENSP00000252729.2	Q9BXT2
	CACNG6	ENST00000955412.1		c.38G>A	p.Arg13Gln	missense	Exon 1 of 3	ENSP00000625471.1
	CACNG6	ENST00000346968.2	TSL:5	c.38G>A	p.Arg13Gln	missense	Exon 1 of 3	ENSP00000319097.2	A6NFR2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 99288 AF XY: 0.00

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: 8.00e-7 AC: 1 AN: 1250338 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 610406

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25302

American (AMR) AF: 0.00 AC: 0 AN: 17726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16724

East Asian (EAS) AF: 0.00 AC: 0 AN: 31044

South Asian (SAS) AF: 0.00 AC: 0 AN: 46946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4922

European-Non Finnish (NFE) AF: 9.88e-7 AC: 1 AN: 1012518

Other (OTH) AF: 0.00 AC: 0 AN: 50676

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M
PhyloP100		4.3
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.091
Sift	Benign	0.26	T
Sift4G	Benign	0.42	T
Polyphen		0.61	P
Vest4		0.17
MutPred		0.14		Loss of MoRF binding (P = 0.0707)
MVP		0.38
MPC		1.4
ClinPred		0.75	D
GERP RS		3.1
PromoterAI		0.0012	Neutral
Varity_R		0.067
gMVP		0.37
Mutation Taster		=94/6	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: rs1434492187; hg19: chr19-54496169;