6-142421522-T-C

Variant names:

• chr6-142421522-T-C
• rs6929442
• NM_198569.3:c.3319+1418T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000367609.8(ADGRG6):​c.3319+1418T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,036 control chromosomes in the GnomAD database, including 13,586 homozygotes. 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: 𝑓 0.40 (13586 hom., cov: 32)
• Consequence: ADGRG6 ENST00000367609.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 8 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367609.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG6	NM_198569.3	MANE Select	c.3319+1418T>C		intron	N/A	NP_940971.2
	ADGRG6	NM_001032395.3		c.3235+1418T>C		intron	N/A	NP_001027567.2
	ADGRG6	NM_020455.6		c.3319+1418T>C		intron	N/A	NP_065188.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG6	ENST00000367609.8	TSL:1 MANE Select	c.3319+1418T>C		intron	N/A	ENSP00000356581.3
	ADGRG6	ENST00000367608.6	TSL:1	c.3235+1418T>C		intron	N/A	ENSP00000356580.2
	ADGRG6	ENST00000230173.10	TSL:1	c.3319+1418T>C		intron	N/A	ENSP00000230173.6

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60122 AN: 151918 Hom.: 13555 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.420

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.396 AC: 60212 AN: 152036 Hom.: 13586 Cov.: 32 AF XY: 0.393 AC XY: 29205 AN XY: 74318

African (AFR) AF: 0.624 AC: 25896 AN: 41472

American (AMR) AF: 0.356 AC: 5431 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1144 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2092 AN: 5164

South Asian (SAS) AF: 0.328 AC: 1581 AN: 4814

European-Finnish (FIN) AF: 0.268 AC: 2828 AN: 10564

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19967 AN: 67974

Other (OTH) AF: 0.421 AC: 890 AN: 2112

Alfa AF: 0.395 Hom.: 6737

Bravo AF: 0.410

Asia WGS AF: 0.434 AC: 1506 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.81
PhyloP100		1.0
Mutation Taster		=100/0	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: rs6929442; hg19: chr6-142742659;