Variant chr11-110137039-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033390.2(ZC3H12C):c.398G>T(p.Arg133Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZC3H12C
NM_033390.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.433

Variant links:

Genes affected

ZC3H12C (HGNC:29362): (zinc finger CCCH-type containing 12C) Predicted to enable endoribonuclease activity and mRNA binding activity. Predicted to be involved in RNA phosphodiester bond hydrolysis, endonucleolytic. Predicted to be active in cytoplasmic ribonucleoprotein granule and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZC3H12C links:

RDX (HGNC:9944): (radixin) Radixin is a cytoskeletal protein that may be important in linking actin to the plasma membrane. It is highly similar in sequence to both ezrin and moesin. The radixin gene has been localized by fluorescence in situ hybridization to 11q23. A truncated version representing a pseudogene (RDXP2) was assigned to Xp21.3. Another pseudogene that seemed to lack introns (RDXP1) was mapped to 11p by Southern and PCR analyses. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

RDX links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05551839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H12C	NM_033390.2 link	c.398G>T	p.Arg133Leu	missense_variant	2/6	ENST00000278590.8	NP_203748.1	Q9C0D7-1
ZC3H12C	NM_001411037.1 link	c.401G>T	p.Arg134Leu	missense_variant	2/6		NP_001397966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZC3H12C	ENST00000278590.8 link	c.398G>T	p.Arg133Leu	missense_variant	2/6	2	NM_033390.2	ENSP00000278590.3	Q9C0D7-1
ZC3H12C	ENST00000528673.5 link	c.401G>T	p.Arg134Leu	missense_variant	2/6	2		ENSP00000431821.1	Q9C0D7-2
ZC3H12C	ENST00000453089.2 link	c.305G>T	p.Arg102Leu	missense_variant	1/5	2		ENSP00000413094.2	E9PP00
RDX	ENST00000645527.1 link	n.*251-5309C>A		intron_variant				ENSP00000496121.1	A0A2R8Y7M3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

247844

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134476

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461478

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

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

May 09, 2023

The c.398G>T (p.R133L) alteration is located in exon 2 (coding exon 2) of the ZC3H12C gene. This alteration results from a G to T substitution at nucleotide position 398, causing the arginine (R) at amino acid position 133 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

M;.;.

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.61

N;N;N

REVEL

Benign

0.055

Sift

Uncertain

0.026

D;D;D

Sift4G

Uncertain

0.034

D;D;D

Polyphen

0.033

B;.;.

Vest4

0.40

MutPred

0.31

Gain of helix (P = 0.0325);.;.;

MVP

0.043

MPC

0.041

ClinPred

0.12

GERP RS

2.3

Varity_R

0.061

gMVP

0.17

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