chr3-71784983-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001126128.2(PROK2):​c.70G>A​(p.Ala24Thr) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. A24P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PROK2
NM_001126128.2 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.447
Variant links:
Genes affected
PROK2 (HGNC:18455): (prokineticin 2) This gene encodes a protein expressed in the suprachiasmatic nucleus (SCN) circadian clock that may function as the output component of the circadian clock. The secreted form of the encoded protein may also serve as a chemoattractant for neuronal precursor cells in the olfactory bulb. Proteins from other vertebrates which are similar to this gene product were isolated based on homology to snake venom and secretions from frog skin, and have been shown to have diverse functions. Mutations in this gene are associated with Kallmann syndrome 4. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30452263).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PROK2NM_001126128.2 linkc.70G>A p.Ala24Thr missense_variant Exon 1 of 4 ENST00000295619.4 NP_001119600.1 Q9HC23-1
PROK2NM_021935.4 linkc.70G>A p.Ala24Thr missense_variant Exon 1 of 3 NP_068754.1 Q9HC23-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PROK2ENST00000295619.4 linkc.70G>A p.Ala24Thr missense_variant Exon 1 of 4 1 NM_001126128.2 ENSP00000295619.3 Q9HC23-1
PROK2ENST00000353065.7 linkc.70G>A p.Ala24Thr missense_variant Exon 1 of 3 1 ENSP00000295618.3 Q9HC23-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1097556
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
520986
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
0.90
DANN
Benign
0.95
DEOGEN2
Benign
0.34
.;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.072
N
LIST_S2
Benign
0.20
T;T
M_CAP
Pathogenic
0.92
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
1.1
L;L
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-0.46
N;N
REVEL
Benign
0.22
Sift
Benign
0.52
T;T
Sift4G
Benign
0.41
T;T
Polyphen
0.32
.;B
Vest4
0.092
MutPred
0.40
Gain of phosphorylation at A24 (P = 0.0592);Gain of phosphorylation at A24 (P = 0.0592);
MVP
0.54
MPC
0.10
ClinPred
0.089
T
GERP RS
-1.8
Varity_R
0.034
gMVP
0.41

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.

Other links and lift over

dbSNP: rs587777863; hg19: chr3-71834134; API