Variant chr16-88577296-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_144604.4(ZC3H18):c.173C>T(p.Pro58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000546 in 1,612,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00055 ( 0 hom. )

Consequence

ZC3H18
NM_144604.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.978

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008488178).

BP6

Variant 16-88577296-C-T is Benign according to our data. Variant chr16-88577296-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2302081.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 76 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H18	NM_144604.4 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant	2/18	ENST00000301011.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZC3H18	ENST00000301011.10 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant	2/18	1	NM_144604.4	P1
ZC3H18	ENST00000452588.6 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant	2/19	2
ZC3H18	ENST00000569435.5 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant	2/6	5

Frequencies

GnomAD3 genomes

AF:

0.000500

AC:

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

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:

0.000544

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000294

AC:

AN:

248286

Hom.:

AF XY:

0.000268

AC XY:

AN XY:

134430

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000518

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.000551

AC:

804

AN:

1460240

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

381

AN XY:

726288

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000630

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000751

Gnomad4 NFE exome

AF:

0.000663

Gnomad4 OTH exome

AF:

0.000481

GnomAD4 genome

AF:

0.000500

AC:

AN:

152018

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00223

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000575

Hom.:

Bravo

AF:

0.00103

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000313

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.6

DANN

Benign

0.41

DEOGEN2

Benign

0.023

T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.0085

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.0

N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.33

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.065

MVP

0.043

MPC

0.018

ClinPred

0.0019

GERP RS

0.50

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.016

gMVP

0.020

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