19-53914503-G-T

Variant names:

• chr19-53914503-G-T
• rs747198707
• NM_031896.5:c.200G>T

Variant summary

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

The NM_031896.5(CACNG7):​c.200G>T​(p.Arg67Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R67Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2575475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG7	NM_031896.5	c.200G>T	p.Arg67Leu	missense_variant	Exon 3 of 6	ENST00000391767.6	NP_114102.2
CACNG7	NM_001384801.1	c.200G>T	p.Arg67Leu	missense_variant	Exon 3 of 5		NP_001371730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG7	ENST00000391767.6	c.200G>T	p.Arg67Leu	missense_variant	Exon 3 of 6	5	NM_031896.5	ENSP00000375647.1
CACNG7	ENST00000222212.6	c.200G>T	p.Arg67Leu	missense_variant	Exon 2 of 5	1		ENSP00000222212.2
CACNG7	ENST00000391766.1	c.200G>T	p.Arg67Leu	missense_variant	Exon 2 of 4	1		ENSP00000375646.1
CACNG7	ENST00000468076.5	n.184-862G>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461678 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727144

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.200G>T (p.R67L) alteration is located in exon 2 (coding exon 2) of the CACNG7 gene. This alteration results from a G to T substitution at nucleotide position 200, causing the arginine (R) at amino acid position 67 to be replaced by a leucine (L). 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	Benign	0.14
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	.;D;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.23	N;N;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.0060	B;B;.
Vest4		0.61
MutPred		0.55		Loss of MoRF binding (P = 0.0064);Loss of MoRF binding (P = 0.0064);Loss of MoRF binding (P = 0.0064);
MVP		0.47
MPC		1.1
ClinPred		0.42	T
GERP RS		3.1
Varity_R		0.098
gMVP		0.82

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: rs747198707; hg19: chr19-54417757;