NM_198569.3:c.688A>C

Variant names:

• chr6-142370412-A-C
• rs11155242
• NM_198569.3:c.688A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198569.3(ADGRG6):​c.688A>C​(p.Lys230Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,612,652 control chromosomes in the GnomAD database, including 30,493 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.20 (3068 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27425 hom.)
• Consequence: ADGRG6 NM_198569.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015581548).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.688A>C	p.Lys230Gln	missense_variant	Exon 4 of 25	ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8	c.688A>C	p.Lys230Gln	missense_variant	Exon 4 of 25	1	NM_198569.3	ENSP00000356581.3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30259 AN: 152056 Hom.: 3061 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.186 AC: 46028 AN: 247820 Hom.: 4535 AF XY: 0.189 AC XY: 25385 AN XY: 134396

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.0943

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.193

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.191 AC: 278740 AN: 1460478 Hom.: 27425 Cov.: 33 AF XY: 0.192 AC XY: 139210 AN XY: 726510

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.199 AC: 30307 AN: 152174 Hom.: 3068 Cov.: 32 AF XY: 0.199 AC XY: 14790 AN XY: 74408

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.0951

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.213

Alfa AF: 0.195 Hom.: 7486

Bravo AF: 0.196

TwinsUK AF: 0.185 AC: 686

ALSPAC AF: 0.175 AC: 676

ESP6500AA AF: 0.208 AC: 761

ESP6500EA AF: 0.194 AC: 1586

ExAC AF: 0.187 AC: 22556

Asia WGS AF: 0.210 AC: 726 AN: 3478

EpiCase AF: 0.196

EpiControl AF: 0.208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.9
DANN	Benign	0.47
DEOGEN2	Benign	0.067	T;.;.;.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.76	T;T;T;T;T
MetaRNN	Benign	0.0016	T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.080	N;N;N;N;N
REVEL	Benign	0.053
Sift	Benign	0.57	T;T;T;T;T
Sift4G	Benign	0.20	.;.;.;.;T
Polyphen		0.0080	B;B;B;B;B
Vest4		0.053
MPC		0.13
ClinPred		0.0071	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.57

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: rs11155242; hg19: chr6-142691549; COSMIC: COSV51588591; COSMIC: COSV51588591;