NM_032119.4:c.4786G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032119.4(ADGRV1):​c.4786G>T​(p.Val1596Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,496 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1596I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

3
12
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.23

Publications

1 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADGRV1NM_032119.4 linkc.4786G>T p.Val1596Phe missense_variant Exon 22 of 90 ENST00000405460.9 NP_115495.3 Q8WXG9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADGRV1ENST00000405460.9 linkc.4786G>T p.Val1596Phe missense_variant Exon 22 of 90 1 NM_032119.4 ENSP00000384582.2 Q8WXG9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461496
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727030
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33470
American (AMR)
AF:
0.0000224
AC:
1
AN:
44698
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39678
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53400
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111744
Other (OTH)
AF:
0.00
AC:
0
AN:
60368
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32
ExAC
AF:
0.00000828
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;T;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.90
.;D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.49
T;T;T
MetaSVM
Uncertain
-0.23
T
PhyloP100
4.2
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-2.8
.;D;.
REVEL
Uncertain
0.34
Sift
Uncertain
0.0020
.;D;.
Sift4G
Uncertain
0.0040
.;D;.
Polyphen
0.99
D;D;.
Vest4
0.81
MutPred
0.46
Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);.;
MVP
0.79
MPC
0.36
ClinPred
0.98
D
GERP RS
4.9
Varity_R
0.67
gMVP
0.91
Mutation Taster
=62/38
polymorphism

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

Other links and lift over

dbSNP: rs371179945; hg19: chr5-89968396; API