Variant 19-3151782-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002068.4(GNA15):c.561G>A(p.Met187Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00775 in 1,612,794 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 59 hom. )

Consequence

GNA15
NM_002068.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.874

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009044021).

BP6

Variant 19-3151782-G-A is Benign according to our data. Variant chr19-3151782-G-A is described in ClinVar as [Benign]. Clinvar id is 790433.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 1108 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA15	NM_002068.4 linkuse as main transcript	c.561G>A	p.Met187Ile	missense_variant	4/7	ENST00000262958.4
GNA15-DT	NR_110670.1 linkuse as main transcript	n.159-1992C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GNA15	ENST00000262958.4 linkuse as main transcript	c.561G>A	p.Met187Ile	missense_variant	4/7	1	NM_002068.4	P1
GNA15-DT	ENST00000587587.1 linkuse as main transcript	n.159-1992C>T		intron_variant, non_coding_transcript_variant		2
GNA15	ENST00000586082.1 linkuse as main transcript	n.522G>A		non_coding_transcript_exon_variant	2/3	3
GNA15	ENST00000592455.1 linkuse as main transcript	c.*591G>A		3_prime_UTR_variant, NMD_transcript_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.00728

AC:

1108

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.0302

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00997

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00727

AC:

1818

AN:

250164

Hom.:

AF XY:

0.00710

AC XY:

961

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.0274

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0139

Gnomad NFE exome

AF:

0.00933

Gnomad OTH exome

AF:

0.00936

GnomAD4 exome

AF:

0.00780

AC:

11390

AN:

1460446

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

5555

AN XY:

726526

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.00376

Gnomad4 ASJ exome

AF:

0.0278

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0147

Gnomad4 NFE exome

AF:

0.00821

Gnomad4 OTH exome

AF:

0.00845

GnomAD4 genome

AF:

0.00727

AC:

1108

AN:

152348

Hom.:

Cov.:

AF XY:

0.00738

AC XY:

550

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.0302

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.00997

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00892

Hom.:

Bravo

AF:

0.00639

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0116

AC:

100

ExAC

AF:

0.00689

AC:

836

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00916

EpiControl

AF:

0.00932

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.15

MetaRNN

Benign

0.0090

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.67

REVEL

Benign

0.13

Sift

Benign

0.065

Sift4G

Benign

0.11

Vest4

0.47

MutPred

0.65

Gain of catalytic residue at M187 (P = 0.077);

MVP

0.32

MPC

0.83

ClinPred

0.023

GERP RS

4.6

gMVP

0.45

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