Genetic Variant NM_032119.4:c.11178T>A (chr5-90753630-T-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_032119.4(ADGRV1):c.11178T>A(p.Asp3726Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.47

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.746

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.11178T>A	p.Asp3726Glu	missense	Exon 54 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.11194T>A		non_coding_transcript_exon	Exon 54 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.11178T>A	p.Asp3726Glu	missense	Exon 54 of 90	ENSP00000384582.2
ADGRV1	ENST00000509621.1	TSL:1	n.3875T>A		non_coding_transcript_exon	Exon 22 of 26
ADGRV1	ENST00000425867.3	TSL:5	c.309T>A	p.Asp103Glu	missense	Exon 3 of 38	ENSP00000392618.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Benign

0.14

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.72

PhyloP100

1.5

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.33

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.035

Polyphen

0.98

Vest4

0.73

MutPred

0.73

Loss of helix (P = 0.079)

MVP

0.62

MPC

0.29

ClinPred

0.98

GERP RS

3.2

Varity_R

0.36

gMVP

0.85

Mutation Taster

=58/42

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over