6-142367819-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_198569.3(ADGRG6):c.354A>G(p.Leu118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,613,870 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (18 hom.)
• Consequence: ADGRG6 NM_198569.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.642

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 6-142367819-A-G is Benign according to our data. Variant chr6-142367819-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 791451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.642 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00161 (2346/1461518) while in subpopulation MID AF= 0.0267 (154/5768). AF 95% confidence interval is 0.0233. There are 18 homozygotes in gnomad4_exome. There are 1407 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG6	NM_198569.3	c.354A>G	p.Leu118=	synonymous_variant	3/25	ENST00000367609.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG6	ENST00000367609.8	c.354A>G	p.Leu118=	synonymous_variant	3/25	1	NM_198569.3

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 182 AN: 152234 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00682

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00153

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00213 AC: 529 AN: 248826 Hom.: 3 AF XY: 0.00267 AC XY: 361 AN XY: 134960

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.000957

Gnomad ASJ exome AF: 0.00229

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00794

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00181

Gnomad OTH exome AF: 0.00398

GnomAD4 exome AF: 0.00161 AC: 2346 AN: 1461518 Hom.: 18 Cov.: 31 AF XY: 0.00194 AC XY: 1407 AN XY: 727052

Gnomad4 AFR exome AF: 0.000717

Gnomad4 AMR exome AF: 0.000984

Gnomad4 ASJ exome AF: 0.00165

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00851

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00109

Gnomad4 OTH exome AF: 0.00215

GnomAD4 genome AF: 0.00117 AC: 179 AN: 152352 Hom.: 0 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74496

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00642

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00153

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00169 Hom.: 1

Bravo AF: 0.00111

Asia WGS AF: 0.00260 AC: 10 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00320

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	ADGRG6: BP4, BP7, BS2 -

Lethal congenital contracture syndrome 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 29, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	5.9
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs140723393; hg19: chr6-142688956;