16-88577617-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_144604.4(ZC3H18):​c.494A>T​(p.Glu165Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZC3H18
NM_144604.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07110202).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZC3H18NM_144604.4 linkuse as main transcriptc.494A>T p.Glu165Val missense_variant 2/18 ENST00000301011.10 NP_653205.3 Q86VM9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZC3H18ENST00000301011.10 linkuse as main transcriptc.494A>T p.Glu165Val missense_variant 2/181 NM_144604.4 ENSP00000301011.5 Q86VM9
ZC3H18ENST00000452588.6 linkuse as main transcriptc.494A>T p.Glu165Val missense_variant 2/192 ENSP00000416951.2 E7ERS3
ZC3H18ENST00000569435.5 linkuse as main transcriptc.252+242A>T intron_variant 5 ENSP00000455260.1 H3BPD0

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
250230
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135570
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461618
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
727102
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
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
AF:
0.00000657
AC:
1
AN:
152128
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

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 GeneticsSep 13, 2023The c.494A>T (p.E165V) alteration is located in exon 2 (coding exon 1) of the ZC3H18 gene. This alteration results from a A to T substitution at nucleotide position 494, causing the glutamic acid (E) at amino acid position 165 to be replaced by a valine (V). 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
0.11
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
17
DANN
Benign
0.95
DEOGEN2
Benign
0.23
T;.
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.66
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.76
T;T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.071
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L;.
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-3.2
D;D
REVEL
Benign
0.11
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.041
D;T
Polyphen
0.0010
B;B
Vest4
0.15
MutPred
0.24
Loss of solvent accessibility (P = 0.0146);Loss of solvent accessibility (P = 0.0146);
MVP
0.043
MPC
0.019
ClinPred
0.25
T
GERP RS
0.10
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
3.2
Varity_R
0.10
gMVP
0.039

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: rs776625358; hg19: chr16-88644025; API