19-53942191-C-G

Variant names:

• chr19-53942191-C-G
• rs1240074850
• NM_031896.5:c.726C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031896.5(CACNG7):​c.726C>G​(p.Ser242Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,786 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: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CACNG7 NM_031896.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33

Genes affected

CACNG7 (HGNC:13626): (calcium voltage-gated channel auxiliary subunit gamma 7) The protein encoded by this gene is a type II 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 I TARP and a calcium channel gamma subunit. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34780228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG7	NM_031896.5	c.726C>G	p.Ser242Arg	missense_variant	Exon 6 of 6	ENST00000391767.6	NP_114102.2
CACNG7	NM_001384801.1	c.580C>G	p.Pro194Ala	missense_variant	Exon 5 of 5		NP_001371730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG7	ENST00000391767.6	c.726C>G	p.Ser242Arg	missense_variant	Exon 6 of 6	5	NM_031896.5	ENSP00000375647.1
CACNG7	ENST00000222212.6	c.726C>G	p.Ser242Arg	missense_variant	Exon 5 of 5	1		ENSP00000222212.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461786 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727214

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: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.726C>G (p.S242R) alteration is located in exon 5 (coding exon 5) of the CACNG7 gene. This alteration results from a C to G substitution at nucleotide position 726, causing the serine (S) at amino acid position 242 to be replaced by an arginine (R). 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	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.079
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.73	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;D
Vest4		0.42
MutPred		0.32		Loss of phosphorylation at S242 (P = 0.0101);Loss of phosphorylation at S242 (P = 0.0101);
MVP		0.26
MPC		2.0
ClinPred		0.99	D
GERP RS		1.7
Varity_R		0.43
gMVP		0.89

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

LitVar

Other links and lift over

dbSNP: rs1240074850; hg19: chr19-54445445;