rs878927192

Variant names:

• chr19-53963306-C-G
• rs878927192
• NM_031895.6:c.164C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-53963306-C-G
• chr19-53963306-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031895.6(CACNG8):​c.164C>G​(p.Thr55Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CACNG8 NM_031895.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36607018).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031895.6. 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
	CACNG8	NM_031895.6	MANE Select	c.164C>G	p.Thr55Ser	missense	Exon 1 of 4	NP_114101.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG8	ENST00000270458.4	TSL:1 MANE Select	c.164C>G	p.Thr55Ser	missense	Exon 1 of 4	ENSP00000270458.3	Q8WXS5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455072 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724180

African (AFR) AF: 0.0000302 AC: 1 AN: 33166

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.00 AC: 0 AN: 86102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111006

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.21
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.7
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.21
Sift	Benign	0.12	T
Sift4G	Benign	0.17	T
Polyphen		0.91	P
Vest4		0.14
MutPred		0.46		Gain of disorder (P = 0.1136)
MVP		0.37
ClinPred		0.83	D
GERP RS		3.5
PromoterAI		0.0066	Neutral
Varity_R		0.47
gMVP		0.81

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: rs878927192; hg19: chr19-54466560;