4-39185730-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025132.4(WDR19):​c.11T>C​(p.Ile4Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

WDR19
NM_025132.4 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59
Variant links:
Genes affected
WDR19 (HGNC:18340): (WD repeat domain 19) The protein encoded by this gene is a member of the WD (tryptophan-aspartic acid) repeat family, which is a large family of structurally-related proteins known to participate in a wide range of cellular processes. Each WD repeat typically contains about 40 amino acids that are usually bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides. This protein contains six WD repeats, three transmembrane domains, and a clathrin heavy-chain repeat. Mutations in this gene have been described in individuals with a wide range of disorders affecting function of the cilium. These disorders are known as ciliopathies, and include Jeune syndrome, Sensenbrenner syndromes, Senior-Loken syndrome, combined or isolated nephronophthisis (NPHP), and retinitis pigmentosa (RP). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2554097).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR19NM_025132.4 linkuse as main transcriptc.11T>C p.Ile4Thr missense_variant 2/37 ENST00000399820.8 NP_079408.3 Q8NEZ3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR19ENST00000399820.8 linkuse as main transcriptc.11T>C p.Ile4Thr missense_variant 2/371 NM_025132.4 ENSP00000382717.3 Q8NEZ3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Asphyxiating thoracic dystrophy 5;C4225376:Senior-Loken syndrome 8 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 01, 2021This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 4 of the WDR19 protein (p.Ile4Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with WDR19-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.55
BayesDel_addAF
Benign
-0.039
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.43
T;.
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.82
T;T
M_CAP
Uncertain
0.097
D
MetaRNN
Benign
0.26
T;T
MetaSVM
Benign
-0.53
T
MutationAssessor
Benign
1.4
L;.
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-2.9
D;D
REVEL
Benign
0.20
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
0.020
B;P
Vest4
0.31
MutPred
0.40
Loss of catalytic residue at I4 (P = 0.0135);Loss of catalytic residue at I4 (P = 0.0135);
MVP
0.77
MPC
0.23
ClinPred
0.97
D
GERP RS
5.4
Varity_R
0.34
gMVP
0.35

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.

Other links and lift over

hg19: chr4-39187350; API