rs200241873

Variant names:

• chr16-57650313-C-G
• rs200241873
• NM_201525.4:c.26C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-57650313-C-G
• chr16-57650313-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201525.4(ADGRG1):​c.26C>G​(p.Thr9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T9M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ADGRG1 NM_201525.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.49
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• bilateral frontoparietal polymicrogyria

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07217014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG1	NM_201525.4	c.26C>G	p.Thr9Arg	missense_variant	Exon 2 of 14	ENST00000562631.7	NP_958933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG1	ENST00000562631.7	c.26C>G	p.Thr9Arg	missense_variant	Exon 2 of 14	1	NM_201525.4	ENSP00000455351.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461158 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726922

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111362

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	0.0020
DANN	Benign	0.61
DEOGEN2	Benign	0.11	.;.;.;.;.;.;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;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.79	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
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.072	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;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-4.5
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.45	N;D;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;D;N;D;N;N;N;N;N;N;N;N;.;D;N;N;N;N;N;N;N;N;N;N;N;N;D;N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.11	T;.;T;T;D;T;T;D;D;T;D;D;D;D;D;D;D;T;D;T;D;T;D;T;D;T;T;D;.;D;.;D;D;D;D;T;T;D;T;.;.;D;D;D;T;D;D;T;D;D;D;T;D;.;D;D;D;D;T
Sift4G	Benign	0.25	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;T;T;T;T
Polyphen		0.0	.;.;.;.;.;B;B;.;.;B;.;.;.;.;.;.;.;.;.;B;.;.;.;.;.;B;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.18, 0.16, 0.16, 0.16, 0.18, 0.17, 0.17, 0.17
MutPred		0.40		Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);Loss of catalytic residue at F12 (P = 0.1663);
MVP		0.73
ClinPred		0.066	T
GERP RS		-7.6
Varity_R		0.051
gMVP		0.94

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: rs200241873; hg19: chr16-57684225;