Variant 16-88586624-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144604.4(ZC3H18):c.628G>A(p.Val210Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZC3H18
NM_144604.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.46

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4135601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H18	NM_144604.4 linkuse as main transcript	c.628G>A	p.Val210Met	missense_variant	3/18	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.628G>A	p.Val210Met	missense_variant	3/18	1	NM_144604.4	ENSP00000301011.5	Q86VM9
ZC3H18	ENST00000452588.6 linkuse as main transcript	c.628G>A	p.Val210Met	missense_variant	3/19	2		ENSP00000416951.2	E7ERS3
ZC3H18	ENST00000567085.1 linkuse as main transcript	c.7G>A	p.Val3Met	missense_variant	1/6	5		ENSP00000455083.1	H3BP01
ZC3H18	ENST00000569435.5 linkuse as main transcript	c.277G>A	p.Val93Met	missense_variant	3/6	5		ENSP00000455260.1	H3BPD0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 07, 2024

The c.628G>A (p.V210M) alteration is located in exon 3 (coding exon 2) of the ZC3H18 gene. This alteration results from a G to A substitution at nucleotide position 628, causing the valine (V) at amino acid position 210 to be replaced by a methionine (M). 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

Pathogenic

0.96

BayesDel_addAF

Benign

0.00028

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.81

L;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.025

D;D;D

Sift4G

Uncertain

0.010

D;T;D

Polyphen

1.0

D;D;.

Vest4

0.66

MutPred

0.16

Loss of methylation at K211 (P = 0.0196);Loss of methylation at K211 (P = 0.0196);.;

MVP

0.11

MPC

1.9

ClinPred

0.95

GERP RS

5.0

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.9

Varity_R

0.24

gMVP

0.25

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over