Variant X-65488991-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001010888.4(ZC3H12B):c.190G>A(p.Asp64Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000413 in 1,209,380 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000043 ( 0 hom. 19 hem. )

Consequence

ZC3H12B
NM_001010888.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.290

Variant links:

Genes affected

ZC3H12B (HGNC:17407): (zinc finger CCCH-type containing 12B) The protein encoded by this gene belongs to a family of CCCH-type zinc finger proteins that are involved in the proinflammatory activation of macrophages. The exact function of this family member is unknown, but it is thought to function as a ribonuclease. [provided by RefSeq, May 2010]

ZC3H12B links:

LAS1L (HGNC:25726): (LAS1 like ribosome biogenesis factor) Enables RNA binding activity. Predicted to be involved in maturation of 5.8S rRNA and maturation of LSU-rRNA. Located in membrane. Part of MLL1 complex. Implicated in Wilson-Turner syndrome. [provided by Alliance of Genome Resources, Apr 2022]

LAS1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06286931).

BS2

High Hemizygotes in GnomAdExome4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H12B	NM_001010888.4 linkuse as main transcript	c.190G>A	p.Asp64Asn	missense_variant	6/10	ENST00000338957.5	NP_001010888.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H12B	ENST00000338957.5 linkuse as main transcript	c.190G>A	p.Asp64Asn	missense_variant	6/10	1	NM_001010888.4	ENSP00000340839	P1	Q5HYM0-1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111364

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33562

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.0000166

AC:

AN:

180931

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

67007

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

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:

0.0000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000428

AC:

AN:

1098016

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

363448

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.0000546

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111364

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33562

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000188

Gnomad4 OTH

AF:

0.00134

Bravo

AF:

0.0000189

ExAC

AF:

0.00000826

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

Jan 25, 2023

The c.190G>A (p.D64N) alteration is located in exon 1 (coding exon 1) of the ZC3H12B gene. This alteration results from a G to A substitution at nucleotide position 190, causing the aspartic acid (D) at amino acid position 64 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

0.070

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-1.0

CADD

Benign

6.5

DANN

Benign

0.96

DEOGEN2

Benign

0.0028

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.59

M_CAP

Benign

0.0023

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.43

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

0.010

REVEL

Benign

0.021

Sift

Benign

0.23

Sift4G

Benign

0.53

Vest4

0.11

MVP

0.068

MPC

0.49

ClinPred

0.032

GERP RS

0.053

Varity_R

0.053

gMVP

0.086

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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