Variant 16-88577225-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_144604.4(ZC3H18):c.102C>T(p.Ser34Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,612,538 control chromosomes in the GnomAD database, including 161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 11 hom., cov: 31)

Exomes 𝑓: 0.013 ( 150 hom. )

Consequence

ZC3H18
NM_144604.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.59

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 16-88577225-C-T is Benign according to our data. Variant chr16-88577225-C-T is described in ClinVar as [Benign]. Clinvar id is 782142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.59 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0128 (18739/1461030) while in subpopulation NFE AF= 0.0159 (17646/1111582). AF 95% confidence interval is 0.0157. There are 150 homozygotes in gnomad4_exome. There are 8861 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1226 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H18	NM_144604.4 linkuse as main transcript	c.102C>T	p.Ser34Ser	synonymous_variant	2/18	ENST00000301011.10	NP_653205.3	Q86VM9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZC3H18	ENST00000301011.10 linkuse as main transcript	c.102C>T	p.Ser34Ser	synonymous_variant	2/18	1	NM_144604.4	ENSP00000301011.5	Q86VM9
ZC3H18	ENST00000452588.6 linkuse as main transcript	c.102C>T	p.Ser34Ser	synonymous_variant	2/19	2		ENSP00000416951.2	E7ERS3
ZC3H18	ENST00000569435.5 linkuse as main transcript	c.102C>T	p.Ser34Ser	synonymous_variant	2/6	5		ENSP00000455260.1	H3BPD0

Frequencies

GnomAD3 genomes

AF:

0.00811

AC:

1228

AN:

151392

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.00817

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.000959

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.00867

GnomAD3 exomes

AF:

0.00674

AC:

1685

AN:

250090

Hom.:

AF XY:

0.00673

AC XY:

911

AN XY:

135298

show subpopulations

Gnomad AFR exome

AF:

0.00210

Gnomad AMR exome

AF:

0.00439

Gnomad ASJ exome

AF:

0.00180

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.000880

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.00690

GnomAD4 exome

AF:

0.0128

AC:

18739

AN:

1461030

Hom.:

150

Cov.:

AF XY:

0.0122

AC XY:

8861

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.00221

Gnomad4 AMR exome

AF:

0.00433

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00148

Gnomad4 NFE exome

AF:

0.0159

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.00809

AC:

1226

AN:

151508

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

500

AN XY:

73942

show subpopulations

Gnomad4 AFR

AF:

0.00279

Gnomad4 AMR

AF:

0.00816

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.000959

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.00858

Alfa

AF:

0.00913

Hom.:

Bravo

AF:

0.00817

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0153

EpiControl

AF:

0.0137

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 14, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.2

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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