6-142408187-T-G

Position:

• chr6-142408187-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM5 PP3

The NM_198569.3(ADGRG6):​c.2306T>G​(p.Val769Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V769E) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRG6 NM_198569.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.49

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 Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr6-142408187-T-A is described in Lovd as [Pathogenic].
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.2306T>G	p.Val769Gly	missense_variant	16/25	ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8	c.2306T>G	p.Val769Gly	missense_variant	16/25	1	NM_198569.3	ENSP00000356581

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D;.;.;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	T;T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.81	D;D;D;D
MetaSVM	Benign	-0.38	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-6.6	D;D;D;D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D;D;D;D
Polyphen		0.98	D;D;D;D
Vest4		0.67
MutPred		0.58		Loss of stability (P = 0.023);.;.;Loss of stability (P = 0.023);
MVP		0.81
MPC		0.62
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.91
gMVP		0.93

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: rs793888525; hg19: chr6-142729324;