chr14-88572197-T-A

Variant summary

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

The NM_024824.5(ZC3H14):​c.403T>A​(p.Ser135Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZC3H14
NM_024824.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83
Variant links:
Genes affected
ZC3H14 (HGNC:20509): (zinc finger CCCH-type containing 14) The protein encoded by this gene is a poly(A)-binding protein that can affect gene expression and poly(A) tail length. The encoded protein may influence mRNA stability, nuclear export, and translation. [provided by RefSeq, May 2016]

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=0.109567285).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZC3H14NM_024824.5 linkc.403T>A p.Ser135Thr missense_variant Exon 5 of 17 ENST00000251038.10 NP_079100.2 Q6PJT7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZC3H14ENST00000251038.10 linkc.403T>A p.Ser135Thr missense_variant Exon 5 of 17 1 NM_024824.5 ENSP00000251038.5 Q6PJT7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461882
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727244
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
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
Sep 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.403T>A (p.S135T) alteration is located in exon 5 (coding exon 5) of the ZC3H14 gene. This alteration results from a T to A substitution at nucleotide position 403, causing the serine (S) at amino acid position 135 to be replaced by a threonine (T). 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
Benign
0.080
BayesDel_addAF
Benign
-0.013
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
22
DANN
Benign
0.75
DEOGEN2
Benign
0.027
T;.;.;T;T;.;.;.;.
Eigen
Benign
-0.055
Eigen_PC
Benign
0.015
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.89
D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.11
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
1.8
L;L;.;.;.;L;L;.;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.77
N;N;N;N;N;N;N;N;N
REVEL
Benign
0.13
Sift
Benign
0.25
T;D;T;D;D;T;D;D;D
Sift4G
Benign
0.18
T;T;T;T;T;T;T;T;T
Polyphen
0.33
B;P;.;.;.;.;.;.;.
Vest4
0.30
MutPred
0.12
Gain of glycosylation at S134 (P = 0.0458);Gain of glycosylation at S134 (P = 0.0458);Gain of glycosylation at S134 (P = 0.0458);.;.;Gain of glycosylation at S134 (P = 0.0458);Gain of glycosylation at S134 (P = 0.0458);.;.;
MVP
0.068
MPC
0.073
ClinPred
0.47
T
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-89038541; API