chr6-68639307-C-G

Position:

• chr6-68639307-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001704.3(ADGRB3):​c.632C>G​(p.Ser211Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 3.65

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRB3	NM_001704.3	c.632C>G	p.Ser211Trp	missense_variant	3/32	ENST00000370598.6	NP_001695.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRB3	ENST00000370598.6	c.632C>G	p.Ser211Trp	missense_variant	3/32	1	NM_001704.3	ENSP00000359630	P1
ADGRB3	ENST00000546190.5	c.632C>G	p.Ser211Trp	missense_variant	1/30	1		ENSP00000441821	P1
ADGRB3	ENST00000684661.1	c.632C>G	p.Ser211Trp	missense_variant, NMD_transcript_variant	3/32			ENSP00000507613

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.632C>G (p.S211W) alteration is located in exon 3 (coding exon 1) of the ADGRB3 gene. This alteration results from a C to G substitution at nucleotide position 632, causing the serine (S) at amino acid position 211 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	.;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.11
Sift	Uncertain	0.025	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.83	P;P
Vest4		0.71
MutPred		0.59		Gain of catalytic residue at S211 (P = 0.2005);Gain of catalytic residue at S211 (P = 0.2005);
MVP		0.043
MPC		0.95
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.22
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-69349199;