19-53992950-G-A

Variant names:

• chr19-53992950-G-A
• rs780619316
• NM_145814.2:c.73G>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.73G>A​(p.Gly25Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000399 in 1,251,984 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: CACNG6 NM_145814.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798
• 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=0.12236428).

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.73G>A	p.Gly25Arg	missense	Exon 1 of 4	NP_665813.1	Q9BXT2
	CACNG6	NM_145815.2		c.73G>A	p.Gly25Arg	missense	Exon 1 of 3	NP_665814.1	A6NFR2
	CACNG6	NM_031897.3		c.73G>A	p.Gly25Arg	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.73G>A	p.Gly25Arg	missense	Exon 1 of 4	ENSP00000252729.2	Q9BXT2
	CACNG6	ENST00000955412.1		c.73G>A	p.Gly25Arg	missense	Exon 1 of 3	ENSP00000625471.1
	CACNG6	ENST00000346968.2	TSL:5	c.73G>A	p.Gly25Arg	missense	Exon 1 of 3	ENSP00000319097.2	A6NFR2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 35606 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: 0.00000399 AC: 5 AN: 1251984 Hom.: 0 Cov.: 31 AF XY: 0.00000492 AC XY: 3 AN XY: 609976

African (AFR) AF: 0.00 AC: 0 AN: 25164

American (AMR) AF: 0.00 AC: 0 AN: 11828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16986

East Asian (EAS) AF: 0.00 AC: 0 AN: 29544

South Asian (SAS) AF: 0.00 AC: 0 AN: 54258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5022

European-Non Finnish (NFE) AF: 0.00000394 AC: 4 AN: 1014730

Other (OTH) AF: 0.0000195 AC: 1 AN: 51156

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000214 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.80
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.043
Sift	Benign	0.050	D
Sift4G	Uncertain	0.052	T
Polyphen		0.75	P
Vest4		0.051
MutPred		0.21		Gain of helix (P = 0.0225)
MVP		0.29
MPC		1.2
ClinPred		0.44	T
GERP RS		2.4
PromoterAI		-0.00050	Neutral
Varity_R		0.060
gMVP		0.43
Mutation Taster		=90/10	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: rs780619316; hg19: chr19-54496204;