rs9389983

Variant names:

• chr6-142312607-T-C
• rs9389983
• NM_198569.3:c.103+2963T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198569.3(ADGRG6):​c.103+2963T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 151,910 control chromosomes in the GnomAD database, including 34,078 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 0.64 (34078 hom., cov: 32)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.103+2963T>C		intron_variant	Intron 2 of 24	ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8	c.103+2963T>C		intron_variant	Intron 2 of 24	1	NM_198569.3	ENSP00000356581.3

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97826 AN: 151792 Hom.: 34017 Cov.: 32

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.645 AC: 97941 AN: 151910 Hom.: 34078 Cov.: 32 AF XY: 0.644 AC XY: 47817 AN XY: 74230

African (AFR) AF: 0.913 AC: 37871 AN: 41502

American (AMR) AF: 0.620 AC: 9441 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1789 AN: 3458

East Asian (EAS) AF: 0.801 AC: 4134 AN: 5158

South Asian (SAS) AF: 0.624 AC: 3000 AN: 4810

European-Finnish (FIN) AF: 0.486 AC: 5127 AN: 10542

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34607 AN: 67896

Other (OTH) AF: 0.651 AC: 1373 AN: 2110

Alfa AF: 0.551 Hom.: 38294

Bravo AF: 0.665

Asia WGS AF: 0.718 AC: 2494 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.046
DANN	Benign	0.41
PhyloP100		-3.0
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: rs9389983; hg19: chr6-142633744;