Variant chr16-57567477-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001304376.3(ADGRG5):c.707C>T(p.Ser236Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,456,432 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ADGRG5
NM_001304376.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.854

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG5	NM_001304376.3 linkuse as main transcript	c.707C>T	p.Ser236Phe	missense_variant	8/12	ENST00000349457.8	NP_001291305.1
LOC105371291	XR_933627.4 linkuse as main transcript	n.959G>A		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.707C>T	p.Ser236Phe	missense_variant	8/12	1	NM_001304376.3	ENSP00000290823	P1
ADGRG5	ENST00000340339.4 linkuse as main transcript	c.707C>T	p.Ser236Phe	missense_variant	8/12	1		ENSP00000342981	P1
ADGRG5	ENST00000394361.8 linkuse as main transcript	n.793C>T		non_coding_transcript_exon_variant	8/11	2
ADGRG5	ENST00000564607.1 linkuse as main transcript	n.2240C>T		non_coding_transcript_exon_variant	7/11	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247712

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134240

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1456432

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724776

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Dec 17, 2023

The c.707C>T (p.S236F) alteration is located in exon 8 (coding exon 7) of the ADGRG5 gene. This alteration results from a C to T substitution at nucleotide position 707, causing the serine (S) at amino acid position 236 to be replaced by a phenylalanine (F). 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

0.26

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.81

.;T

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Uncertain

-0.11

MutationTaster

Benign

0.85

D;D

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.33

MutPred

0.55

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.44

MPC

0.72

ClinPred

0.98

GERP RS

4.0

Varity_R

0.31

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

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