chr6-142309560-C-A

Variant names:

• chr6-142309560-C-A
• rs749355583
• NM_198569.3:c.19C>A

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.19C>A​(p.Arg7Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADGRG6 NM_198569.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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=-0.53).
• BP7: Synonymous conserved (PhyloP=0.178 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.19C>A	p.Arg7Arg	synonymous	Exon 2 of 25	NP_940971.2
	ADGRG6	NM_001032395.3		c.19C>A	p.Arg7Arg	synonymous	Exon 2 of 24	NP_001027567.2
	ADGRG6	NM_020455.6		c.19C>A	p.Arg7Arg	synonymous	Exon 2 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.19C>A	p.Arg7Arg	synonymous	Exon 2 of 25	ENSP00000356581.3
	ADGRG6	ENST00000367608.6	TSL:1	c.19C>A	p.Arg7Arg	synonymous	Exon 2 of 24	ENSP00000356580.2
	ADGRG6	ENST00000230173.10	TSL:1	c.19C>A	p.Arg7Arg	synonymous	Exon 2 of 26	ENSP00000230173.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456334 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 724036

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39568

South Asian (SAS) AF: 0.00 AC: 0 AN: 85260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108924

Other (OTH) AF: 0.00 AC: 0 AN: 60138

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.7
DANN	Benign	0.79
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs749355583; hg19: chr6-142630697;