chr6-142302064-C-T

Variant names:

• chr6-142302064-C-T
• rs77043049
• NM_198569.3:c.-266C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198569.3(ADGRG6):​c.-266C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00706 in 537,340 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (83 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (19 hom.)
• Consequence: ADGRG6 NM_198569.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.904
• Publications: 0 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

ENSG00000310391 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 6-142302064-C-T is Benign according to our data. Variant chr6-142302064-C-T is described in ClinVar as Benign. ClinVar VariationId is 1256800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0567 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.-266C>T		5_prime_UTR	Exon 1 of 25	NP_940971.2	Q86SQ4-3
	ADGRG6	NM_001032395.3		c.-266C>T		5_prime_UTR	Exon 1 of 24	NP_001027567.2	Q86SQ4-4
	ADGRG6	NM_020455.6		c.-266C>T		5_prime_UTR	Exon 1 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.-266C>T		5_prime_UTR	Exon 1 of 25	ENSP00000356581.3	Q86SQ4-3
	ADGRG6	ENST00000367608.6	TSL:1	c.-266C>T		5_prime_UTR	Exon 1 of 24	ENSP00000356580.2	Q86SQ4-4
	ADGRG6	ENST00000230173.10	TSL:1	c.-266C>T		5_prime_UTR	Exon 1 of 26	ENSP00000230173.6	Q86SQ4-1

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2626 AN: 152224 Hom.: 83 Cov.: 33

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00739

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00300 AC: 1156 AN: 384998 Hom.: 19 Cov.: 1 AF XY: 0.00316 AC XY: 637 AN XY: 201624

African (AFR) AF: 0.0555 AC: 554 AN: 9978

American (AMR) AF: 0.00660 AC: 86 AN: 13032

Ashkenazi Jewish (ASJ) AF: 0.0000815 AC: 1 AN: 12264

East Asian (EAS) AF: 0.00 AC: 0 AN: 27070

South Asian (SAS) AF: 0.00988 AC: 306 AN: 30966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28316

Middle Eastern (MID) AF: 0.00504 AC: 9 AN: 1784

European-Non Finnish (NFE) AF: 0.000344 AC: 82 AN: 238456

Other (OTH) AF: 0.00510 AC: 118 AN: 23132

GnomAD4 genome AF: 0.0173 AC: 2636 AN: 152342 Hom.: 83 Cov.: 33 AF XY: 0.0167 AC XY: 1242 AN XY: 74494

African (AFR) AF: 0.0586 AC: 2438 AN: 41578

American (AMR) AF: 0.00738 AC: 113 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00911 AC: 44 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68030

Other (OTH) AF: 0.0114 AC: 24 AN: 2112

Alfa AF: 0.0138 Hom.: 7

Bravo AF: 0.0195

Asia WGS AF: 0.00924 AC: 33 AN: 3478

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	-0.74
CADD	Benign	9.8
DANN	Benign	0.74
PhyloP100		0.90
PromoterAI		-0.086	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	polymorphism

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: rs77043049; hg19: chr6-142623201;