Variant 11-110137168-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_033390.2(ZC3H12C):c.527A>G(p.Glu176Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZC3H12C
NM_033390.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.94

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:

Genome browser will be placed here

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=0.41725716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H12C	NM_033390.2 linkuse as main transcript	c.527A>G	p.Glu176Gly	missense_variant	2/6	ENST00000278590.8	NP_203748.1	Q9C0D7-1
ZC3H12C	NM_001411037.1 linkuse as main transcript	c.530A>G	p.Glu177Gly	missense_variant	2/6		NP_001397966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZC3H12C	ENST00000278590.8 linkuse as main transcript	c.527A>G	p.Glu176Gly	missense_variant	2/6	2	NM_033390.2	ENSP00000278590.3	Q9C0D7-1
ZC3H12C	ENST00000528673.5 linkuse as main transcript	c.530A>G	p.Glu177Gly	missense_variant	2/6	2		ENSP00000431821.1	Q9C0D7-2
ZC3H12C	ENST00000453089.2 linkuse as main transcript	c.434A>G	p.Glu145Gly	missense_variant	1/5	2		ENSP00000413094.2	E9PP00
RDX	ENST00000645527.1 linkuse as main transcript	n.*251-5438T>C		intron_variant				ENSP00000496121.1	A0A2R8Y7M3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000804

AC:

AN:

248638

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134870

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461552

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727032

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 15, 2023

The c.527A>G (p.E176G) alteration is located in exon 2 (coding exon 2) of the ZC3H12C gene. This alteration results from a A to G substitution at nucleotide position 527, causing the glutamic acid (E) at amino acid position 176 to be replaced by a glycine (G). 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

Uncertain

0.34

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

T;.;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0085

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.99

D;.;.

Vest4

0.83

MutPred

0.39

Loss of helix (P = 0.0237);.;.;

MVP

0.068

MPC

0.074

ClinPred

0.73

GERP RS

5.5

Varity_R

0.14

gMVP

0.46

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