6-142367905-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.699

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]

ACMG classification

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	UniProt
ADGRG6	NM_198569.3	c.440T>A	p.Ile147Asn	missense_variant	3/25	ENST00000367609.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG6	ENST00000367609.8	c.440T>A	p.Ile147Asn	missense_variant	3/25	1	NM_198569.3

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3350 AN: 152158 Hom.: 114 Cov.: 32

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.: 40 AF XY: 0.00521 AC XY: 681 AN XY: 130630

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.: 28 AF XY: 0.00236 AC XY: 1693 AN XY: 718182

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.: 32 AF XY: 0.0208 AC XY: 1549 AN XY: 74462

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.: 17

Bravo AF: 0.0257

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0744 AC: 282

ESP6500EA AF: 0.000607 AC: 5

ExAC AF: 0.00730 AC: 882

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Benign	0.074	T;.;.;.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
MetaRNN	Benign	0.0030	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.18	N;N;N;N;N
REVEL	Benign	0.035
Sift	Uncertain	0.0060	D;D;D;D;T
Polyphen		0.28	B;B;B;B;P
Vest4		0.29
MVP		0.18
MPC		0.23
ClinPred		0.015	T
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

Other links and lift over

dbSNP: rs75679810; hg19: chr6-142689042;