19-53982172-T-A

Variant names:

• chr19-53982172-T-A
• NM_031895.6:c.601T>A

Variant summary

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

The NM_031895.6(CACNG8):​c.601T>A​(p.Ser201Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CACNG8 NM_031895.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.672

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG8	NM_031895.6	c.601T>A	p.Ser201Thr	missense_variant	Exon 4 of 4	ENST00000270458.4	NP_114101.4
MIR935	NR_030632.1	n.-135T>A		upstream_gene_variant
MIR935	unassigned_transcript_3404	n.-190T>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG8	ENST00000270458.4	c.601T>A	p.Ser201Thr	missense_variant	Exon 4 of 4	1	NM_031895.6	ENSP00000270458.3
MIR935	ENST00000401179.1	n.-135T>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.601T>A (p.S201T) alteration is located in exon 4 (coding exon 4) of the CACNG8 gene. This alteration results from a T to A substitution at nucleotide position 601, causing the serine (S) at amino acid position 201 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	.;D
Eigen	Benign	0.16
Eigen_PC	Benign	0.065
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Pathogenic	0.59	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.0	N;.
REVEL	Uncertain	0.54
Sift	Benign	0.11	T;.
Sift4G	Uncertain	0.010	D;.
Polyphen		0.93	.;P
Vest4		0.36
MutPred		0.58		Loss of catalytic residue at S201 (P = 0.0273);Loss of catalytic residue at S201 (P = 0.0273);
MVP		0.70
ClinPred		0.95	D
GERP RS		2.1
Varity_R		0.12
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr19-54485426;