chr16-88577328-G-A

Variant summary

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

The NM_144604.4(ZC3H18):​c.205G>A​(p.Glu69Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000329 in 1,609,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

ZC3H18
NM_144604.4 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12
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=0.15033972).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZC3H18NM_144604.4 linkuse as main transcriptc.205G>A p.Glu69Lys missense_variant 2/18 ENST00000301011.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZC3H18ENST00000301011.10 linkuse as main transcriptc.205G>A p.Glu69Lys missense_variant 2/181 NM_144604.4 P1
ZC3H18ENST00000452588.6 linkuse as main transcriptc.205G>A p.Glu69Lys missense_variant 2/192
ZC3H18ENST00000569435.5 linkuse as main transcriptc.205G>A p.Glu69Lys missense_variant 2/65

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152148
Hom.:
0
Cov.:
31
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:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000407
AC:
10
AN:
245864
Hom.:
0
AF XY:
0.0000301
AC XY:
4
AN XY:
132888
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000117
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000336
Gnomad FIN exome
AF:
0.0000472
Gnomad NFE exome
AF:
0.0000361
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000323
AC:
47
AN:
1457030
Hom.:
0
Cov.:
31
AF XY:
0.0000331
AC XY:
24
AN XY:
724352
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000113
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000234
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.0000352
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152148
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

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 GeneticsJan 10, 2022The c.205G>A (p.E69K) alteration is located in exon 2 (coding exon 1) of the ZC3H18 gene. This alteration results from a G to A substitution at nucleotide position 205, causing the glutamic acid (E) at amino acid position 69 to be replaced by a lysine (K). 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
0.088
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.048
T;.;T
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.87
D;D;D
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.5
N;N;N
REVEL
Benign
0.063
Sift
Uncertain
0.0070
D;D;D
Sift4G
Benign
0.32
T;T;T
Polyphen
0.97
D;D;.
Vest4
0.46
MVP
0.043
MPC
0.019
ClinPred
0.23
T
GERP RS
4.6
Varity_R
0.067
gMVP
0.057

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: rs369582517; hg19: chr16-88643736; COSMIC: COSV105186047; API