Variant chr16-57566692-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001304376.3(ADGRG5):c.640C>G(p.Pro214Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000745 in 1,591,260 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00077 ( 1 hom. )

Consequence

ADGRG5
NM_001304376.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.512

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03785175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG5	NM_001304376.3 linkuse as main transcript	c.640C>G	p.Pro214Ala	missense_variant	7/12	ENST00000349457.8	NP_001291305.1
LOC105371291	XR_933627.4 linkuse as main transcript	n.1744G>C		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.640C>G	p.Pro214Ala	missense_variant	7/12	1	NM_001304376.3	ENSP00000290823	P1
ADGRG5	ENST00000340339.4 linkuse as main transcript	c.640C>G	p.Pro214Ala	missense_variant	7/12	1		ENSP00000342981	P1
ADGRG5	ENST00000394361.8 linkuse as main transcript	n.726C>G		non_coding_transcript_exon_variant	7/11	2
ADGRG5	ENST00000564607.1 linkuse as main transcript	n.2173C>G		non_coding_transcript_exon_variant	6/11	2

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000529

AC:

122

AN:

230516

Hom.:

AF XY:

0.000544

AC XY:

AN XY:

124938

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.0000337

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000682

Gnomad NFE exome

AF:

0.000986

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.000767

AC:

1103

AN:

1438964

Hom.:

Cov.:

AF XY:

0.000715

AC XY:

511

AN XY:

715092

show subpopulations

Gnomad4 AFR exome

AF:

0.0000927

Gnomad4 AMR exome

AF:

0.0000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000877

Gnomad4 NFE exome

AF:

0.000925

Gnomad4 OTH exome

AF:

0.000555

GnomAD4 genome

AF:

0.000538

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.000971

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000348

Hom.:

Bravo

AF:

0.000540

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000758

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.640C>G (p.P214A) alteration is located in exon 7 (coding exon 6) of the ADGRG5 gene. This alteration results from a C to G substitution at nucleotide position 640, causing the proline (P) at amino acid position 214 to be replaced by an alanine (A). 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

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.65

.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.12

Sift

Benign

0.37

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.98

D;D

Vest4

0.31

MVP

0.40

MPC

0.25

ClinPred

0.023

GERP RS

2.4

Varity_R

0.069

gMVP

0.21

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

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