chr16-88598669-C-T

Variant summary

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

The NM_144604.4(ZC3H18):​c.887C>T​(p.Pro296Leu) 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

ZC3H18
NM_144604.4 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.09
Variant links:
Genes affected
ZC3H18 (HGNC:25091): (zinc finger CCCH-type containing 18) Enables mRNA cap binding complex binding activity and protein-macromolecule adaptor activity. Involved in RNA destabilization. Located in nuclear speck. Part of ribonucleoprotein complex. [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 UniProt
ZC3H18NM_144604.4 linkuse as main transcriptc.887C>T p.Pro296Leu missense_variant 5/18 ENST00000301011.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZC3H18ENST00000301011.10 linkuse as main transcriptc.887C>T p.Pro296Leu missense_variant 5/181 NM_144604.4 P1
ZC3H18ENST00000452588.6 linkuse as main transcriptc.959C>T p.Pro320Leu missense_variant 6/192
ZC3H18ENST00000567085.1 linkuse as main transcriptc.269C>T p.Pro90Leu missense_variant 3/65
ZC3H18ENST00000569435.5 linkuse as main transcriptc.536C>T p.Pro179Leu missense_variant 5/65

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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 GeneticsJun 02, 2023The c.887C>T (p.P296L) alteration is located in exon 5 (coding exon 4) of the ZC3H18 gene. This alteration results from a C to T substitution at nucleotide position 887, causing the proline (P) at amino acid position 296 to be replaced by a leucine (L). 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
Pathogenic
0.62
BayesDel_addAF
Uncertain
0.057
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T;.;T
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.45
T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.4
L;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-3.7
D;D;D
REVEL
Benign
0.24
Sift
Benign
0.051
T;D;T
Sift4G
Uncertain
0.025
D;D;T
Polyphen
1.0
D;D;.
Vest4
0.70
MutPred
0.20
.;Loss of glycosylation at P320 (P = 0.0025);.;
MVP
0.068
MPC
0.37
ClinPred
1.0
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.40
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs928864889; hg19: chr16-88665077; API