16-57565149-T-G

Position:

• chr16-57565149-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001304376.3(ADGRG5):​c.545T>G​(p.Leu182Arg) variant causes a missense, splice region 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. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRG5 NM_001304376.3 missense, splice_region
• Scores: Splicing: ADA: 0.9144
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09

Genes affected

ADGRG5 (HGNC:19010): (adhesion G protein-coupled receptor G5) This gene encodes a member of the adhesion family of G-protein coupled receptors. Members of this family are characterized by long N-termini and multiple functional domains. They may play a role in the immune system as well as in the central nervous system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3558799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG5	NM_001304376.3	c.545T>G	p.Leu182Arg	missense_variant, splice_region_variant	6/12	ENST00000349457.8	NP_001291305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG5	ENST00000349457.8	c.545T>G	p.Leu182Arg	missense_variant, splice_region_variant	6/12	1	NM_001304376.3	ENSP00000290823	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

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

Jan 19, 2024

The c.545T>G (p.L182R) alteration is located in exon 6 (coding exon 5) of the ADGRG5 gene. This alteration results from a T to G substitution at nucleotide position 545, causing the leucine (L) at amino acid position 182 to be replaced by an arginine (R). 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	0.23
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T;.;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.28	.;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	0.98	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N;.;N
REVEL	Benign	0.21
Sift	Benign	0.048	D;.;D
Sift4G	Uncertain	0.033	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.51
MutPred		0.56		Gain of solvent accessibility (P = 0.0062);Gain of solvent accessibility (P = 0.0062);Gain of solvent accessibility (P = 0.0062);
MVP		0.35
MPC		0.84
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.27
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.91
dbscSNV1_RF	Pathogenic	0.78
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: chr16-57599061;