19-53914545-C-G

Variant names:

• chr19-53914545-C-G
• rs369839062
• NM_031896.5:c.242C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_031896.5(CACNG7):​c.242C>G​(p.Pro81Arg) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P81L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CACNG7 NM_031896.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.6455 (below the threshold of 3.09). Trascript score misZ: 1.8969 (below the threshold of 3.09).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031896.5. 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
	CACNG7	NM_031896.5	MANE Select	c.242C>G	p.Pro81Arg	missense	Exon 3 of 6	NP_114102.2
	CACNG7	NM_001384801.1		c.242C>G	p.Pro81Arg	missense	Exon 3 of 5	NP_001371730.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG7	ENST00000391767.6	TSL:5 MANE Select	c.242C>G	p.Pro81Arg	missense	Exon 3 of 6	ENSP00000375647.1	P62955
	CACNG7	ENST00000222212.6	TSL:1	c.242C>G	p.Pro81Arg	missense	Exon 2 of 5	ENSP00000222212.2	P62955
	CACNG7	ENST00000391766.1	TSL:1	c.242C>G	p.Pro81Arg	missense	Exon 2 of 4	ENSP00000375646.1	A0A0C4DFY2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.034
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.34
Sift	Benign	0.13	T
Sift4G	Benign	0.19	T
Polyphen		0.89	P
Vest4		0.59
MVP		0.73
MPC		1.2
ClinPred		0.70	D
GERP RS		3.1
Varity_R		0.14
gMVP		0.90
Mutation Taster		=52/48	polymorphism

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: rs369839062; hg19: chr19-54417799;