chr1-151404881-T-C

Variant summary

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

The NM_015100.4(POGZ):​c.4154A>G​(p.His1385Arg) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1385Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

POGZ
NM_015100.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89
Variant links:
Genes affected
POGZ (HGNC:18801): (pogo transposable element derived with ZNF domain) The protein encoded by this gene appears to be a zinc finger protein containing a transposase domain at the C-terminus. This protein was found to interact with the transcription factor SP1 in a yeast two-hybrid system. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Aug 2010]

Genome browser will be placed here

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=0.16530293).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POGZNM_015100.4 linkc.4154A>G p.His1385Arg missense_variant Exon 19 of 19 ENST00000271715.7 NP_055915.2 Q7Z3K3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POGZENST00000271715.7 linkc.4154A>G p.His1385Arg missense_variant Exon 19 of 19 1 NM_015100.4 ENSP00000271715.2 Q7Z3K3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
May 09, 2017
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The p.H1385R variant (also known as c.4154A>G), located in coding exon 18 of the POGZ gene, results from an A to G substitution at nucleotide position 4154. The histidine at codon 1385 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.016
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.022
.;T;.;.;.;.
Eigen
Benign
-0.060
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.92
D;D;D;D;D;D
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.17
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
.;N;.;.;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.74
N;N;N;N;N;N
REVEL
Benign
0.15
Sift
Uncertain
0.020
D;D;D;D;D;D
Sift4G
Benign
0.72
T;T;T;T;T;T
Polyphen
0.25
B;B;P;.;.;P
Vest4
0.32
MutPred
0.14
.;Gain of solvent accessibility (P = 0.0584);.;.;.;.;
MVP
0.64
MPC
0.50
ClinPred
0.46
T
GERP RS
5.3
Varity_R
0.13
gMVP
0.71

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: rs1557861908; hg19: chr1-151377357; API