18-76851850-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001306089.2(ZNF236):​c.274G>T​(p.Gly92Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZNF236
NM_001306089.2 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05
Variant links:
Genes affected
ZNF236 (HGNC:13028): (zinc finger protein 236) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cellular response to glucose stimulus. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF236NM_001306089.2 linkuse as main transcriptc.274G>T p.Gly92Trp missense_variant 3/31 ENST00000320610.14 NP_001293018.1
LOC105372214XR_007066421.1 linkuse as main transcriptn.91-3200C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF236ENST00000320610.14 linkuse as main transcriptc.274G>T p.Gly92Trp missense_variant 3/311 NM_001306089.2 ENSP00000322361 P1

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

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 12, 2023The c.268G>T (p.G90W) alteration is located in exon 3 (coding exon 3) of the ZNF236 gene. This alteration results from a G to T substitution at nucleotide position 268, causing the glycine (G) at amino acid position 90 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Benign
-0.059
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
31
DANN
Uncertain
0.99
DEOGEN2
Benign
0.32
T;T;.
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.46
T;T;T
MetaSVM
Benign
-0.51
T
MutationAssessor
Pathogenic
3.7
.;H;.
MutationTaster
Benign
0.92
N;N
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-3.7
.;D;.
REVEL
Benign
0.24
Sift
Uncertain
0.0050
.;D;.
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
0.98
.;D;.
Vest4
0.48
MutPred
0.52
.;Loss of disorder (P = 0.0205);Loss of disorder (P = 0.0205);
MVP
0.46
MPC
1.7
ClinPred
0.99
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.32
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: chr18-74563806; API