rs140963173

Positions:

• chr16-57651309-C-G
• chr16-57651309-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001290143.2(ADGRG1):​c.-352C>G variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADGRG1 NM_001290143.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

Genes affected

ADGRG1 (HGNC:4512): (adhesion G protein-coupled receptor G1) This gene encodes a member of the G protein-coupled receptor family and regulates brain cortical patterning. The encoded protein binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ADGRG1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21122897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG1	NM_201525.4	c.174C>G	p.Ile58Met	missense_variant	3/14	ENST00000562631.7	NP_958933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG1	ENST00000562631.7	c.174C>G	p.Ile58Met	missense_variant	3/14	1	NM_201525.4	ENSP00000455351.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251484 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135922

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	.;.;.;.;T;T;T;T;.;T;.;.;.;.;T;.;.;T;T;.;.;.;.;T;.;.;.;T;T;T;.;.;T;T;.;.;T;T;.;T;T;T;T;T;T;T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.86	D;D;D;.;.;D;D;D;D;D;D;D;D;D;.;D;.;D;D;D;.;.;.;D;D;D;D;D;.;D;D;.;.;D;D;D;D;D;D;D;D;.;D;D;D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.74	T
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.9	D;D;D;N;N;D;D;N;D;D;D;D;D;D;D;D;N;D;D;.;D;N;N;D;D;D;D;D;D;D;D;.;D;D;N;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0, 1.0	.;.;.;D;D;.;.;D;.;.;.;.;.;.;.;.;D;.;.;.;.;D;D;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.47, 0.43, 0.43, 0.46, 0.44, 0.45, 0.45
MutPred		0.25		Gain of catalytic residue at I58 (P = 0.0178);.;Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);.;Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);.;.;Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);.;Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);.;.;.;Gain of catalytic residue at I58 (P = 0.0178);.;Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);.;Gain of catalytic residue at I58 (P = 0.0178);.;.;Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);.;Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);Gain of catalytic residue at I58 (P = 0.0178);
MVP		0.92
ClinPred		0.67	D
GERP RS		0.037
Varity_R		0.20
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs140963173; hg19: chr16-57685221;