Variant 16-88577271-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.148G>A(p.Asp50Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ZC3H18
NM_144604.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

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=0.094603926).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H18	NM_144604.4 linkuse as main transcript	c.148G>A	p.Asp50Asn	missense_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.148G>A	p.Asp50Asn	missense_variant	2/18	1	NM_144604.4	ENSP00000301011.5	Q86VM9
ZC3H18	ENST00000452588.6 linkuse as main transcript	c.148G>A	p.Asp50Asn	missense_variant	2/19	2		ENSP00000416951.2	E7ERS3
ZC3H18	ENST00000569435.5 linkuse as main transcript	c.148G>A	p.Asp50Asn	missense_variant	2/6	5		ENSP00000455260.1	H3BPD0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249536

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461324

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726934

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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 26, 2024

The c.148G>A (p.D50N) 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 148, causing the aspartic acid (D) at amino acid position 50 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

0.086

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

T;.;T

Eigen

Benign

-0.070

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.095

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.034

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.025

D;T;D

Polyphen

0.14

B;B;.

Vest4

0.19

MutPred

0.14

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

MVP

0.043

MPC

0.018

ClinPred

0.18

GERP RS

5.6

Varity_R

0.081

gMVP

0.034

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