NM_032119.4:c.15177G>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_032119.4(ADGRV1):c.15177G>T(p.Gln5059His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: -0.728

Publications

0 publications found

Variant links:

Genes affected

ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

ADGRV1 Gene-Disease associations (from GenCC):

Usher syndrome type 2
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 2C
Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
febrile seizures, familial, 4
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ADGRV1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009639651).

BP6

Variant 5-90810437-G-T is Benign according to our data. Variant chr5-90810437-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 289414.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.15177G>T	p.Gln5059His	missense_variant	Exon 74 of 90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 link	c.15177G>T	p.Gln5059His	missense_variant	Exon 74 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000153

AC:

AN:

248768

AF XY:

0.000111

show subpopulations

Gnomad AFR exome

AF:

0.00214

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000541

AC:

AN:

1461538

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727058

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

33478

American (AMR)

AF:

0.000179

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111764

Other (OTH)

AF:

0.000116

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000617

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00204

AC:

AN:

41590

American (AMR)

AF:

0.000392

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000274

Hom.:

Bravo

AF:

0.000620

ESP6500AA

AF:

0.00191

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000166

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:2

Jan 31, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 11, 2017

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 24, 2018

Athena Diagnostics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 12, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Gln5059His in exon 74 of GPR98: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, three mammals (Alpaca, Bactrian camel, Cape elephant shrew) have a histid ine (His) at this position. It has been identified in 0.2% (16/9634) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs201416399). -

ADGRV1-related disorder

Benign:1

Aug 21, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.1

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.081

T;T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.63

.;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.0096

T;T;T

MetaSVM

Benign

-1.1

PhyloP100

-0.73

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.3

.;N;.

REVEL

Benign

0.013

Sift

Benign

0.17

.;T;.

Sift4G

Benign

0.55

.;T;.

Polyphen

0.12

B;B;.

Vest4

0.081

MutPred

0.37

Gain of catalytic residue at N5060 (P = 0.0871);Gain of catalytic residue at N5060 (P = 0.0871);.;

MVP

0.25

MPC

0.10

ClinPred

0.022

GERP RS

0.18

Varity_R

0.048

gMVP

0.43

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over