Variant 19-3148647-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002068.4(GNA15):c.202G>A(p.Ala68Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,589,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

GNA15
NM_002068.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.557

Variant links:

Genes affected

GNA15 (HGNC:4383): (G protein subunit alpha 15) Enables G protein-coupled receptor binding activity. Involved in positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway. Predicted to be located in plasma membrane. Predicted to be part of heterotrimeric G-protein complex. [provided by Alliance of Genome Resources, Apr 2022]

GNA15 links:

GNA15-DT (HGNC:55293): (GNA15 divergent transcript)

GNA15-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023311466).

BS2

High AC in GnomAd at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA15	NM_002068.4 linkuse as main transcript	c.202G>A	p.Ala68Thr	missense_variant	2/7	ENST00000262958.4
GNA15-DT	NR_110670.1 linkuse as main transcript	n.1302C>T		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GNA15	ENST00000262958.4 linkuse as main transcript	c.202G>A	p.Ala68Thr	missense_variant	2/7	1	NM_002068.4	P1
GNA15-DT	ENST00000587587.1 linkuse as main transcript	n.1302C>T		non_coding_transcript_exon_variant	2/4	2
GNA15	ENST00000592455.1 linkuse as main transcript	c.*232G>A		3_prime_UTR_variant, NMD_transcript_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

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:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000197

AC:

AN:

207744

Hom.:

AF XY:

0.000196

AC XY:

AN XY:

112016

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000663

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000559

Gnomad NFE exome

AF:

0.000310

Gnomad OTH exome

AF:

0.000189

GnomAD4 exome

AF:

0.000257

AC:

370

AN:

1436968

Hom.:

Cov.:

AF XY:

0.000253

AC XY:

180

AN XY:

712536

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.0000974

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000533

Gnomad4 NFE exome

AF:

0.000295

Gnomad4 OTH exome

AF:

0.000168

GnomAD4 genome

AF:

0.000223

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000241

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000174

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Jun 11, 2021

The c.202G>A (p.A68T) alteration is located in exon 2 (coding exon 2) of the GNA15 gene. This alteration results from a G to A substitution at nucleotide position 202, causing the alanine (A) at amino acid position 68 to be replaced by a threonine (T). 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

0.070

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Benign

0.93

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.081

M_CAP

Benign

0.060

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.76

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.49

REVEL

Benign

0.080

Sift

Benign

0.17

Sift4G

Benign

0.68

Vest4

0.095

MVP

0.68

MPC

0.58

ClinPred

0.020

GERP RS

0.40

gMVP

0.47

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