Variant 1-67707635-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018841.6(GNG12):c.52G>A(p.Val18Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GNG12
NM_018841.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.33

Variant links:

Genes affected

GNG12 (HGNC:19663): (G protein subunit gamma 12) Enables PDZ domain binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

GNG12 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNG12	NM_018841.6 linkuse as main transcript	c.52G>A	p.Val18Met	missense_variant	3/4	ENST00000370982.4	NP_061329.3	Q9UBI6
GNG12	XM_017001809.3 linkuse as main transcript	c.52G>A	p.Val18Met	missense_variant	3/4		XP_016857298.1	Q9UBI6
GNG12	XM_047425406.1 linkuse as main transcript	c.52G>A	p.Val18Met	missense_variant	4/5		XP_047281362.1
GNG12	XM_047425415.1 linkuse as main transcript	c.52G>A	p.Val18Met	missense_variant	4/5		XP_047281371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNG12	ENST00000370982.4 linkuse as main transcript	c.52G>A	p.Val18Met	missense_variant	3/4	1	NM_018841.6	ENSP00000360021.3		Q9UBI6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246504

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133212

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000302

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:

6.87e-7

AC:

AN:

1455240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000229

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:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.52G>A (p.V18M) alteration is located in exon 3 (coding exon 1) of the GNG12 gene. This alteration results from a G to A substitution at nucleotide position 52, causing the valine (V) at amino acid position 18 to be replaced by a methionine (M). 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

0.78

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Pathogenic

0.68

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.081

MetaRNN

Pathogenic

0.84

MetaSVM

Benign

-0.92

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.74

MutPred

0.70

Gain of disorder (P = 0.0963);

MVP

0.47

MPC

0.70

ClinPred

0.94

GERP RS

6.0

Varity_R

0.61

gMVP

0.74

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over