Variant 6-142367905-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198569.3(ADGRG6):c.440T>A(p.Ile147Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,594,250 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 113 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 121 hom. )

Consequence

ADGRG6
NM_198569.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.699

Variant links:

Genes affected

ADGRG6 (HGNC:13841): (adhesion G protein-coupled receptor G6) This gene, which is upregulated in human umbilical vein endothelial cells, encodes a G protein-coupled receptor. Variations in this gene can affect a person's stature. Multiple transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Mar 2009]

ADGRG6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003043741).

BP6

Variant 6-142367905-T-A is Benign according to our data. Variant chr6-142367905-T-A is described in ClinVar as [Benign]. Clinvar id is 776167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG6	NM_198569.3 linkuse as main transcript	c.440T>A	p.Ile147Asn	missense_variant	3/25	ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8 linkuse as main transcript	c.440T>A	p.Ile147Asn	missense_variant	3/25	1	NM_198569.3	ENSP00000356581		Q86SQ4-3

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3350

AN:

152158

Hom.:

114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0755

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00851

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00647

AC:

1551

AN:

239562

Hom.:

AF XY:

0.00521

AC XY:

681

AN XY:

130630

show subpopulations

Gnomad AFR exome

AF:

0.0782

Gnomad AMR exome

AF:

0.00452

Gnomad ASJ exome

AF:

0.0138

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000198

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000372

Gnomad OTH exome

AF:

0.00305

GnomAD4 exome

AF:

0.00265

AC:

3817

AN:

1441974

Hom.:

121

Cov.:

AF XY:

0.00236

AC XY:

1693

AN XY:

718182

show subpopulations

Gnomad4 AFR exome

AF:

0.0776

Gnomad4 AMR exome

AF:

0.00550

Gnomad4 ASJ exome

AF:

0.0124

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000245

Gnomad4 FIN exome

AF:

0.0000216

Gnomad4 NFE exome

AF:

0.000237

Gnomad4 OTH exome

AF:

0.00623

GnomAD4 genome

AF:

0.0221

AC:

3362

AN:

152276

Hom.:

113

Cov.:

AF XY:

0.0208

AC XY:

1549

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0756

Gnomad4 AMR

AF:

0.00850

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00468

Hom.:

Bravo

AF:

0.0257

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0744

AC:

282

ESP6500EA

AF:

0.000607

AC:

ExAC

AF:

0.00730

AC:

882

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.074

T;.;.;.;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.87

D;D;D;D;D

MetaRNN

Benign

0.0030

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

0.18

N;N;N;N;N

REVEL

Benign

0.035

Sift

Uncertain

0.0060

D;D;D;D;T

Sift4G

Uncertain

0.0040

.;.;.;.;D

Polyphen

0.28

B;B;B;B;P

Vest4

0.29

MVP

0.18

MPC

0.23

ClinPred

0.015

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.46

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