NM_198569.3:c.103+10825T>C

Variant names:

• chr6-142320469-T-C
• rs12189801
• NM_198569.3:c.103+10825T>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+10825T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,074 control chromosomes in the GnomAD database, including 1,173 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 0.11 (1173 hom., cov: 32)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.103+10825T>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+10825T>C		intron_variant	Intron 2 of 24	1	NM_198569.3	ENSP00000356581.3

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16377 AN: 151956 Hom.: 1173 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0798

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.108 AC: 16378 AN: 152074 Hom.: 1173 Cov.: 32 AF XY: 0.106 AC XY: 7869 AN XY: 74340

African (AFR) AF: 0.0264 AC: 1095 AN: 41538

American (AMR) AF: 0.103 AC: 1564 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 494 AN: 3466

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0805 AC: 388 AN: 4820

European-Finnish (FIN) AF: 0.159 AC: 1687 AN: 10588

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10739 AN: 67918

Other (OTH) AF: 0.113 AC: 238 AN: 2114

Alfa AF: 0.143 Hom.: 3073

Bravo AF: 0.0985

Asia WGS AF: 0.0460 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.63
PhyloP100		-0.056
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: rs12189801; hg19: chr6-142641606;