NM_198569.3:c.1138+513C>T

Variant names:

• chr6-142382532-C-T
• rs1040525
• NM_198569.3:c.1138+513C>T

Variant summary

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

The NM_198569.3(ADGRG6):​c.1138+513C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,964 control chromosomes in the GnomAD database, including 14,793 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 0.41 (14793 hom., cov: 33)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG6	NM_198569.3	MANE Select	c.1138+513C>T		intron	N/A	NP_940971.2
	ADGRG6	NM_001032395.3		c.1138+513C>T		intron	N/A	NP_001027567.2
	ADGRG6	NM_020455.6		c.1138+513C>T		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.1138+513C>T		intron	N/A	ENSP00000356581.3
	ADGRG6	ENST00000367608.6	TSL:1	c.1138+513C>T		intron	N/A	ENSP00000356580.2
	ADGRG6	ENST00000230173.10	TSL:1	c.1138+513C>T		intron	N/A	ENSP00000230173.6

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61883 AN: 151846 Hom.: 14753 Cov.: 33

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.408 AC: 61989 AN: 151964 Hom.: 14793 Cov.: 33 AF XY: 0.406 AC XY: 30155 AN XY: 74268

African (AFR) AF: 0.672 AC: 27842 AN: 41462

American (AMR) AF: 0.357 AC: 5449 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1056 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2080 AN: 5180

South Asian (SAS) AF: 0.328 AC: 1579 AN: 4814

European-Finnish (FIN) AF: 0.270 AC: 2848 AN: 10536

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.292 AC: 19813 AN: 67920

Other (OTH) AF: 0.423 AC: 890 AN: 2104

Alfa AF: 0.444 Hom.: 3699

Bravo AF: 0.423

Asia WGS AF: 0.424 AC: 1464 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.63
PhyloP100		0.068
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs1040525; hg19: chr6-142703669;