6-142367690-C-T

Variant names:

• chr6-142367690-C-T
• rs35699755
• NM_198569.3:c.225C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_198569.3(ADGRG6):​c.225C>T​(p.Thr75Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00743 in 1,613,694 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (148 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (283 hom.)
• Consequence: ADGRG6 NM_198569.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.12
• Publications: 5 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 6-142367690-C-T is Benign according to our data. Variant chr6-142367690-C-T is described in ClinVar as Benign. ClinVar VariationId is 1243331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0786 is higher than 0.05.

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>T	p.Thr75Thr	synonymous	Exon 3 of 25	NP_940971.2	Q86SQ4-3
	ADGRG6	NM_001032395.3		c.225C>T	p.Thr75Thr	synonymous	Exon 3 of 24	NP_001027567.2	Q86SQ4-4
	ADGRG6	NM_020455.6		c.225C>T	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>T	p.Thr75Thr	synonymous	Exon 3 of 25	ENSP00000356581.3	Q86SQ4-3
	ADGRG6	ENST00000367608.6	TSL:1	c.225C>T	p.Thr75Thr	synonymous	Exon 3 of 24	ENSP00000356580.2	Q86SQ4-4
	ADGRG6	ENST00000230173.10	TSL:1	c.225C>T	p.Thr75Thr	synonymous	Exon 3 of 26	ENSP00000230173.6	Q86SQ4-1

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3982 AN: 152024 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0807

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.00581

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.0216

GnomAD2 exomes AF: 0.0105 AC: 2615 AN: 249118 AF XY: 0.00895

Gnomad AFR exome AF: 0.0809

Gnomad AMR exome AF: 0.00624

Gnomad ASJ exome AF: 0.00249

Gnomad EAS exome AF: 0.0485

Gnomad FIN exome AF: 0.0000928

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.00744

GnomAD4 exome AF: 0.00547 AC: 7989 AN: 1461552 Hom.: 283 Cov.: 32 AF XY: 0.00530 AC XY: 3850 AN XY: 727062

African (AFR) AF: 0.0861 AC: 2881 AN: 33468

American (AMR) AF: 0.00660 AC: 295 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00210 AC: 55 AN: 26136

East Asian (EAS) AF: 0.0775 AC: 3076 AN: 39696

South Asian (SAS) AF: 0.00318 AC: 274 AN: 86254

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53400

Middle Eastern (MID) AF: 0.00867 AC: 50 AN: 5766

European-Non Finnish (NFE) AF: 0.000679 AC: 755 AN: 1111760

Other (OTH) AF: 0.00994 AC: 600 AN: 60368

GnomAD4 genome AF: 0.0263 AC: 3998 AN: 152142 Hom.: 148 Cov.: 32 AF XY: 0.0252 AC XY: 1876 AN XY: 74384

African (AFR) AF: 0.0809 AC: 3356 AN: 41494

American (AMR) AF: 0.0124 AC: 189 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.0587 AC: 303 AN: 5164

South Asian (SAS) AF: 0.00561 AC: 27 AN: 4812

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10596

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000985 AC: 67 AN: 68010

Other (OTH) AF: 0.0213 AC: 45 AN: 2108

Alfa AF: 0.0135 Hom.: 49

Bravo AF: 0.0302

Asia WGS AF: 0.0330 AC: 115 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.00107

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.85
DANN	Benign	0.67
PhyloP100		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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: rs35699755; hg19: chr6-142688827; COSMIC: COSV51588486;