rs200838029

Variant names:

• chr16-57566656-G-C
• rs200838029
• NM_001304376.3:c.604G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-57566656-G-C
• chr16-57566656-G-T
• chr16-57566656-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001304376.3(ADGRG5):​c.604G>C​(p.Gly202Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,590,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G202W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: ADGRG5 NM_001304376.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20
• Publications: 2 publications found

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]

LOC105371291 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304376.3. 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
	ADGRG5	NM_001304376.3	MANE Select	c.604G>C	p.Gly202Arg	missense	Exon 7 of 12	NP_001291305.1	Q8IZF4
	ADGRG5	NM_153837.4		c.604G>C	p.Gly202Arg	missense	Exon 7 of 12	NP_722579.1	Q8IZF4
	ADGRG5	NM_001318481.2		c.604G>C	p.Gly202Arg	missense	Exon 7 of 11	NP_001305410.1	B4E148

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG5	ENST00000349457.8	TSL:1 MANE Select	c.604G>C	p.Gly202Arg	missense	Exon 7 of 12	ENSP00000290823.4	Q8IZF4
	ADGRG5	ENST00000340339.4	TSL:1	c.604G>C	p.Gly202Arg	missense	Exon 7 of 12	ENSP00000342981.4	Q8IZF4
	ADGRG5	ENST00000897109.1		c.604G>C	p.Gly202Arg	missense	Exon 6 of 11	ENSP00000567168.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000147 AC: 34 AN: 230700 AF XY: 0.000160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000101

Gnomad ASJ exome AF: 0.000111

Gnomad EAS exome AF: 0.000364

Gnomad FIN exome AF: 0.000387

Gnomad NFE exome AF: 0.000131

Gnomad OTH exome AF: 0.000362

GnomAD4 exome AF: 0.000136 AC: 196 AN: 1438078 Hom.: 0 Cov.: 30 AF XY: 0.000157 AC XY: 112 AN XY: 714544

African (AFR) AF: 0.0000308 AC: 1 AN: 32440

American (AMR) AF: 0.000124 AC: 5 AN: 40310

Ashkenazi Jewish (ASJ) AF: 0.000119 AC: 3 AN: 25152

East Asian (EAS) AF: 0.000939 AC: 36 AN: 38354

South Asian (SAS) AF: 0.00 AC: 0 AN: 82798

European-Finnish (FIN) AF: 0.000209 AC: 11 AN: 52644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.000123 AC: 136 AN: 1101326

Other (OTH) AF: 0.0000674 AC: 4 AN: 59370

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152120 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74304

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000255 Hom.: 0

Bravo AF: 0.0000642

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000906 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.085	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.22	D
PhyloP100		3.2
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.81		Gain of MoRF binding (P = 0.0101)
MVP		0.67
MPC		0.77
ClinPred		0.72	D
GERP RS		4.9
Varity_R		0.66
gMVP		0.69
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs200838029; hg19: chr16-57600568;