16-57673374-A-T

Position:

• chr16-57673374-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001308360.2(ADGRG3):​c.-110A>T 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRG3 NM_001308360.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.35

Genes affected

ADGRG3 (HGNC:13728): (adhesion G protein-coupled receptor G3) Predicted to enable G protein-coupled receptor activity. Involved in G protein-coupled receptor signaling pathway and regulation of cell migration. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADGRG3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04415825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG3	NM_170776.5	c.112A>T	p.Met38Leu	missense_variant	2/12	ENST00000333493.9	NP_740746.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG3	ENST00000333493.9	c.112A>T	p.Met38Leu	missense_variant	2/12	1	NM_170776.5	ENSP00000332900.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Nov 17, 2023

The c.112A>T (p.M38L) alteration is located in exon 2 (coding exon 2) of the ADGRG3 gene. This alteration results from a A to T substitution at nucleotide position 112, causing the methionine (M) at amino acid position 38 to be replaced by a leucine (L). 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	Benign	0.11
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0010
DANN	Benign	0.37
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.023
Sift	Benign	0.32	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.18		Loss of helix (P = 0.0626);
MVP		0.030
MPC		0.12
ClinPred		0.56	D
GERP RS		-7.1
Varity_R		0.11
gMVP		0.38

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-57707286;