6-142367690-C-A

Variant names:

• chr6-142367690-C-A
• NM_198569.3:c.225C>A
• ADGRG6 p.Thr75Thr

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_198569.3(ADGRG6):​c.225C>A​(p.Thr75Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T75T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRG6 NM_198569.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• lethal congenital contracture syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-3.12 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198569.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG6	NM_198569.3	MANE Select	c.225C>A	p.Thr75Thr	synonymous	Exon 3 of 25	NP_940971.2	Q86SQ4-3
	ADGRG6	NM_001032395.3		c.225C>A	p.Thr75Thr	synonymous	Exon 3 of 24	NP_001027567.2	Q86SQ4-4
	ADGRG6	NM_020455.6		c.225C>A	p.Thr75Thr	synonymous	Exon 3 of 26	NP_065188.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG6	ENST00000367609.8	TSL:1 MANE Select	c.225C>A	p.Thr75Thr	synonymous	Exon 3 of 25	ENSP00000356581.3	Q86SQ4-3
	ADGRG6	ENST00000367608.6	TSL:1	c.225C>A	p.Thr75Thr	synonymous	Exon 3 of 24	ENSP00000356580.2	Q86SQ4-4
	ADGRG6	ENST00000230173.10	TSL:1	c.225C>A	p.Thr75Thr	synonymous	Exon 3 of 26	ENSP00000230173.6	Q86SQ4-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.36
DANN	Benign	0.62
PhyloP100		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-142688827;