6-68638907-C-T

Variant names:

• chr6-68638907-C-T
• rs1768012589
• NM_001704.3:c.232C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001704.3(ADGRB3):​c.232C>T​(p.Leu78Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRB3 NM_001704.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90
• Publications: 0 publications found

Genes affected

ADGRB3 (HGNC:945): (adhesion G protein-coupled receptor B3) This p53-target gene encodes a brain-specific angiogenesis inhibitor, a seven-span transmembrane protein, and is thought to be a member of the secretin receptor family. Brain-specific angiogenesis proteins BAI2 and BAI3 are similar to BAI1 in structure, have similar tissue specificities, and may also play a role in angiogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.8253 (below the threshold of 3.09). Trascript score misZ: 2.413 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.10629618).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001704.3. 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
	ADGRB3	NM_001704.3	MANE Select	c.232C>T	p.Leu78Phe	missense	Exon 3 of 32	NP_001695.2	O60242-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRB3	ENST00000370598.6	TSL:1 MANE Select	c.232C>T	p.Leu78Phe	missense	Exon 3 of 32	ENSP00000359630.1	O60242-1
	ADGRB3	ENST00000546190.5	TSL:1	c.232C>T	p.Leu78Phe	missense	Exon 1 of 30	ENSP00000441821.2	O60242-1
	ADGRB3	ENST00000684661.1		n.232C>T		non_coding_transcript_exon	Exon 3 of 32	ENSP00000507613.1	A0A804HJR2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.066
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.098
Sift	Benign	0.20	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.21		Gain of sheet (P = 0.0827)
MVP		0.043
MPC		0.23
ClinPred		0.47	T
GERP RS		4.2
PromoterAI		0.011	Neutral
Varity_R		0.062
gMVP		0.26
Mutation Taster		=70/30	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: rs1768012589; hg19: chr6-69348799;