Variant 16-57566681-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001304376.3(ADGRG5):c.629G>A(p.Arg210His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,440,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ADGRG5
NM_001304376.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.66

Variant links:

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]

ADGRG5 links:

LOC105371291 (HGNC:):

LOC105371291 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040959477).

BP6

Variant 16-57566681-G-A is Benign according to our data. Variant chr16-57566681-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3271968.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG5	NM_001304376.3 linkuse as main transcript	c.629G>A	p.Arg210His	missense_variant	7/12	ENST00000349457.8	NP_001291305.1
LOC105371291	XR_933627.4 linkuse as main transcript	n.1755C>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADGRG5	ENST00000349457.8 linkuse as main transcript	c.629G>A	p.Arg210His	missense_variant	7/12	1	NM_001304376.3	ENSP00000290823	P1
ADGRG5	ENST00000340339.4 linkuse as main transcript	c.629G>A	p.Arg210His	missense_variant	7/12	1		ENSP00000342981	P1
ADGRG5	ENST00000394361.8 linkuse as main transcript	n.715G>A		non_coding_transcript_exon_variant	7/11	2
ADGRG5	ENST00000564607.1 linkuse as main transcript	n.2162G>A		non_coding_transcript_exon_variant	6/11	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000216

AC:

AN:

231884

Hom.:

AF XY:

0.0000318

AC XY:

AN XY:

125606

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000670

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000727

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000932

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1440238

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

715846

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000736

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000481

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000816

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.072

DANN

Benign

0.81

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.50

.;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.10

Sift

Benign

0.25

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.0040

B;B

Vest4

0.071

MutPred

0.49

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.081

MPC

0.21

ClinPred

0.033

GERP RS

-8.2

Varity_R

0.018

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over