Variant chr16-57566605-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001304376.3(ADGRG5):c.553T>C(p.Tyr185His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,372,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

ADGRG5
NM_001304376.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.135

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 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=0.26551569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG5	NM_001304376.3 linkuse as main transcript	c.553T>C	p.Tyr185His	missense_variant	7/12	ENST00000349457.8	NP_001291305.1
LOC105371291	XR_933627.4 linkuse as main transcript	n.1831A>G		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.553T>C	p.Tyr185His	missense_variant	7/12	1	NM_001304376.3	ENSP00000290823	P1
ADGRG5	ENST00000340339.4 linkuse as main transcript	c.553T>C	p.Tyr185His	missense_variant	7/12	1		ENSP00000342981	P1
ADGRG5	ENST00000394361.8 linkuse as main transcript	n.639T>C		non_coding_transcript_exon_variant	7/11	2
ADGRG5	ENST00000564607.1 linkuse as main transcript	n.2086T>C		non_coding_transcript_exon_variant	6/11	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.29e-7

AC:

AN:

1372304

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

677382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.35e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 16, 2023

The c.553T>C (p.Y185H) alteration is located in exon 7 (coding exon 6) of the ADGRG5 gene. This alteration results from a T to C substitution at nucleotide position 553, causing the tyrosine (Y) at amino acid position 185 to be replaced by a histidine (H). 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

0.18

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.054

Sift

Benign

0.036

D;D

Sift4G

Benign

0.22

T;T

Polyphen

0.99

D;D

Vest4

0.30

MutPred

0.60

Gain of disorder (P = 0.0896);Gain of disorder (P = 0.0896);

MVP

0.11

MPC

0.28

ClinPred

0.14

GERP RS

2.2

Varity_R

0.12

gMVP

0.44

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over