dbSNP rs369839062: CACNG7:p.Pro81Gln (chr19-53914545-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_031896.5(CACNG7):c.242C>A(p.Pro81Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CACNG7
NM_031896.5 missense

Scores

Clinical Significance

Not reported in ClinVar

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]

CACNG7 links:

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ACMG classification

Classification made for transcript

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
CACNG7	NM_031896.5 link	c.242C>A	p.Pro81Gln	missense_variant	Exon 3 of 6	ENST00000391767.6	NP_114102.2	P62955
CACNG7	NM_001384801.1 link	c.242C>A	p.Pro81Gln	missense_variant	Exon 3 of 5		NP_001371730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNG7	ENST00000391767.6 link	c.242C>A	p.Pro81Gln	missense_variant	Exon 3 of 6	5	NM_031896.5	ENSP00000375647.1	P62955
CACNG7	ENST00000222212.6 link	c.242C>A	p.Pro81Gln	missense_variant	Exon 2 of 5	1		ENSP00000222212.2	P62955
CACNG7	ENST00000391766.1 link	c.242C>A	p.Pro81Gln	missense_variant	Exon 2 of 4	1		ENSP00000375646.1	A0A0C4DFY2
CACNG7	ENST00000468076.5 link	n.184-820C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T;.

Eigen

Benign

-0.053

Eigen_PC

Benign

-0.058

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.91

.;D;D

M_CAP

Benign

0.035

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.1

L;L;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.78

P;P;.

Vest4

0.54

MutPred

0.42

Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);

MVP

0.45

MPC

1.1

ClinPred

0.74

GERP RS

3.1

Varity_R

0.12

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.24

Position offset: 41

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over