Variant 3-120167396-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153002.3(GPR156):c.2081C>T(p.Ala694Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

GPR156
NM_153002.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.366

Variant links:

Genes affected

GPR156 (HGNC:20844): (G protein-coupled receptor 156) G protein-coupled receptors (GPCRs) are a large superfamily of cell surface receptors characterized by 7 helical transmembrane domains, together with N-terminal extracellular and C-terminal intracellular domains.[supplied by OMIM, Mar 2008]

GPR156 links:

LOC105374065 (HGNC:):

LOC105374065 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.070495576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR156	NM_153002.3 linkuse as main transcript	c.2081C>T	p.Ala694Val	missense_variant	10/10	ENST00000464295.6
LOC105374065	XR_924392.3 linkuse as main transcript	n.284-16114G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR156	ENST00000464295.6 linkuse as main transcript	c.2081C>T	p.Ala694Val	missense_variant	10/10	5	NM_153002.3	A2	Q8NFN8-1
GPR156	ENST00000461057.1 linkuse as main transcript	c.2069C>T	p.Ala690Val	missense_variant	9/9	1		P4	Q8NFN8-2
GPR156	ENST00000495912.5 linkuse as main transcript	c.*1144C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250784

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461220

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726816

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:

0.0000252

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000936

Hom.:

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 03, 2022

The c.2081C>T (p.A694V) alteration is located in exon 9 (coding exon 9) of the GPR156 gene. This alteration results from a C to T substitution at nucleotide position 2081, causing the alanine (A) at amino acid position 694 to be replaced by a valine (V). 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

0.085

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.0

DANN

Benign

0.97

DEOGEN2

Benign

0.0025

T;T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.51

T;.;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.90

N;N;N

REVEL

Benign

0.013

Sift

Benign

0.055

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.031

MutPred

0.31

Gain of glycosylation at S691 (P = 0.0065);Gain of glycosylation at S691 (P = 0.0065);.;

MVP

0.048

MPC

0.25

ClinPred

0.038

GERP RS

2.2

Varity_R

0.034

gMVP

0.20

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