19-53914545-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_031896.5(CACNG7):​c.242C>T​(p.Pro81Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,950 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CACNG7
NM_031896.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.39592785).
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNG7NM_031896.5 linkc.242C>T p.Pro81Leu missense_variant Exon 3 of 6 ENST00000391767.6 NP_114102.2 P62955
CACNG7NM_001384801.1 linkc.242C>T p.Pro81Leu missense_variant Exon 3 of 5 NP_001371730.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNG7ENST00000391767.6 linkc.242C>T p.Pro81Leu missense_variant Exon 3 of 6 5 NM_031896.5 ENSP00000375647.1 P62955
CACNG7ENST00000222212.6 linkc.242C>T p.Pro81Leu missense_variant Exon 2 of 5 1 ENSP00000222212.2 P62955
CACNG7ENST00000391766.1 linkc.242C>T p.Pro81Leu missense_variant Exon 2 of 4 1 ENSP00000375646.1 A0A0C4DFY2
CACNG7ENST00000468076.5 linkn.184-820C>T intron_variant Intron 1 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152080
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250400
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135418
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461870
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152080
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 18, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.242C>T (p.P81L) alteration is located in exon 2 (coding exon 2) of the CACNG7 gene. This alteration results from a C to T substitution at nucleotide position 242, causing the proline (P) at amino acid position 81 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
Uncertain
0.35
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.14
T;T;.
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.46
N
LIST_S2
Uncertain
0.95
.;D;D
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.40
T;T;T
MetaSVM
Benign
-0.69
T
MutationAssessor
Benign
1.1
L;L;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.27
Sift
Benign
0.13
T;T;T
Sift4G
Benign
0.31
T;T;T
Polyphen
0.012
B;B;.
Vest4
0.60
MutPred
0.47
Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);
MVP
0.66
MPC
0.86
ClinPred
0.38
T
GERP RS
3.1
Varity_R
0.092
gMVP
0.90

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs369839062; hg19: chr19-54417799; API