19-53963166-C-G

Variant names:

• chr19-53963166-C-G
• NM_031895.6:c.24C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031895.6(CACNG8):​c.24C>G​(p.Asn8Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 30)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CACNG8 NM_031895.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

Genes affected

CACNG8 (HGNC:13628): (calcium voltage-gated channel auxiliary subunit gamma 8) The protein encoded by this gene is a type I 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 II TARP and a calcium channel gamma subunit. The mRNA for this gene is believed to initiate translation from a non-AUG (CUG) start codon. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.120336026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG8	NM_031895.6	c.24C>G	p.Asn8Lys	missense_variant	Exon 1 of 4	ENST00000270458.4	NP_114101.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG8	ENST00000270458.4	c.24C>G	p.Asn8Lys	missense_variant	Exon 1 of 4	1	NM_031895.6	ENSP00000270458.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400312 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 693018

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000204

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.48	T;T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.039
Sift	Uncertain	0.0090	D;.
Sift4G	Uncertain	0.028	D;.
Polyphen		0.14	.;B
Vest4		0.16
MutPred		0.30		Gain of methylation at N8 (P = 0.0036);Gain of methylation at N8 (P = 0.0036);
MVP		0.37
ClinPred		0.40	T
GERP RS		0.55
Varity_R		0.10
gMVP		0.93

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54466420;