19-53982605-G-C

Variant names:

• chr19-53982605-G-C
• rs1399913704
• NM_031895.6:c.1034G>C

Variant summary

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

The NM_031895.6(CACNG8):​c.1034G>C​(p.Gly345Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G345D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CACNG8 NM_031895.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• 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]

MIR935 (HGNC:33678): (microRNA 935) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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=0.10027239).

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.1034G>C	p.Gly345Ala	missense	Exon 4 of 4	NP_114101.4
	MIR935	NR_030632.1		n.*208G>C		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG8	ENST00000270458.4	TSL:1 MANE Select	c.1034G>C	p.Gly345Ala	missense	Exon 4 of 4	ENSP00000270458.3	Q8WXS5
	MIR935	ENST00000401179.1	TSL:6	n.*208G>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 19

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.67
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.35	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.20
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.066
Sift	Benign	0.56	T
Sift4G	Uncertain	0.037	D
Vest4		0.22
MutPred		0.28		Loss of sheet (P = 0.1907)
MVP		0.24
ClinPred		0.055	T
Varity_R		0.20
gMVP		0.25

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: rs1399913704; hg19: chr19-54485859;