Variant 16-88577226-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144604.4(ZC3H18):c.103G>A(p.Asp35Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000217 in 1,613,238 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 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

ZC3H18
NM_144604.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.67

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]

ZC3H18 links:

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=0.113280624).

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H18	NM_144604.4 linkuse as main transcript	c.103G>A	p.Asp35Asn	missense_variant	2/18	ENST00000301011.10	NP_653205.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZC3H18	ENST00000301011.10 linkuse as main transcript	c.103G>A	p.Asp35Asn	missense_variant	2/18	1	NM_144604.4	ENSP00000301011	P1
ZC3H18	ENST00000452588.6 linkuse as main transcript	c.103G>A	p.Asp35Asn	missense_variant	2/19	2		ENSP00000416951
ZC3H18	ENST00000569435.5 linkuse as main transcript	c.103G>A	p.Asp35Asn	missense_variant	2/6	5		ENSP00000455260

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000999

AC:

AN:

250172

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000230

AC:

336

AN:

1461182

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

150

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000288

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0000967

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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 submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.103G>A (p.D35N) 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 103, causing the aspartic acid (D) at amino acid position 35 to be replaced by an asparagine (N). 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

0.096

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.61

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

T;.;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.0099

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

0.64

N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0030

D;D;D

Sift4G

Benign

0.51

T;T;T

Polyphen

0.68

P;P;.

Vest4

0.17

MVP

0.13

MPC

0.018

ClinPred

0.094

GERP RS

5.6

Varity_R

0.089

gMVP

0.031

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over