chr19-53993191-C-T

Variant names:

• chr19-53993191-C-T
• rs1600051480
• NM_145814.2:c.314C>T

Variant summary

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

The NM_145814.2(CACNG6):​c.314C>T​(p.Pro105Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000072 in 1,389,230 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P105S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CACNG6 NM_145814.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.314C>T	p.Pro105Leu	missense	Exon 1 of 4	NP_665813.1	Q9BXT2
	CACNG6	NM_145815.2		c.314C>T	p.Pro105Leu	missense	Exon 1 of 3	NP_665814.1	A6NFR2
	CACNG6	NM_031897.3		c.314C>T	p.Pro105Leu	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.314C>T	p.Pro105Leu	missense	Exon 1 of 4	ENSP00000252729.2	Q9BXT2
	CACNG6	ENST00000955412.1		c.314C>T	p.Pro105Leu	missense	Exon 1 of 3	ENSP00000625471.1
	CACNG6	ENST00000346968.2	TSL:5	c.314C>T	p.Pro105Leu	missense	Exon 1 of 3	ENSP00000319097.2	A6NFR2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1389230 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 685498

African (AFR) AF: 0.00 AC: 0 AN: 31470

American (AMR) AF: 0.00 AC: 0 AN: 35564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25026

East Asian (EAS) AF: 0.00 AC: 0 AN: 35658

South Asian (SAS) AF: 0.00 AC: 0 AN: 79060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5282

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077788

Other (OTH) AF: 0.00 AC: 0 AN: 57786

GnomAD4 genome Cov.: 33

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	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.53	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.58
MutPred		0.55		Gain of stability (P = 0.0318)
MVP		0.85
MPC		0.53
ClinPred		0.99	D
GERP RS		2.5
PromoterAI		0.038	Neutral
Varity_R		0.33
gMVP		0.74
Mutation Taster		=77/23	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: rs1600051480; hg19: chr19-54496445;