chr16-57655971-T-G

Variant names:

• chr16-57655971-T-G
• rs1376041
• NM_201525.4:c.996T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_201525.4(ADGRG1):​c.996T>G​(p.Thr332Thr) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. T332T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADGRG1 NM_201525.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 32 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.183 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201525.4. 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
	ADGRG1	NM_201525.4	MANE Select	c.996T>G	p.Thr332Thr	synonymous	Exon 7 of 14	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.996T>G	p.Thr332Thr	synonymous	Exon 8 of 15	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.996T>G	p.Thr332Thr	synonymous	Exon 8 of 15	NP_001357357.1	Q9Y653-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	ENST00000562631.7	TSL:1 MANE Select	c.996T>G	p.Thr332Thr	synonymous	Exon 7 of 14	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.996T>G	p.Thr332Thr	synonymous	Exon 8 of 15	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.996T>G	p.Thr332Thr	synonymous	Exon 8 of 15	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.2
DANN	Benign	0.46
PhyloP100		-0.18

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: rs1376041; hg19: chr16-57689883;