11-110152933-A-C

Position:

chr11-110152933-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033390.2(ZC3H12C):c.788A>C(p.Glu263Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000416 in 1,612,360 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

ZC3H12C
NM_033390.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H12C	NM_033390.2 link	c.788A>C	p.Glu263Ala	missense_variant	3/6	ENST00000278590.8	NP_203748.1	Q9C0D7-1
ZC3H12C	NM_001411037.1 link	c.791A>C	p.Glu264Ala	missense_variant	3/6		NP_001397966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZC3H12C	ENST00000278590.8 link	c.788A>C	p.Glu263Ala	missense_variant	3/6	2	NM_033390.2	ENSP00000278590.3	Q9C0D7-1
ZC3H12C	ENST00000528673.5 link	c.791A>C	p.Glu264Ala	missense_variant	3/6	2		ENSP00000431821.1	Q9C0D7-2
ZC3H12C	ENST00000453089.2 link	c.695A>C	p.Glu232Ala	missense_variant	2/5	2		ENSP00000413094.2	E9PP00
RDX	ENST00000645527.1 link	n.*251-21203T>G		intron_variant				ENSP00000496121.1	A0A2R8Y7M3

Frequencies

GnomAD3 genomes

AF:

0.000282

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000240

AC:

AN:

246270

Hom.:

AF XY:

0.000277

AC XY:

AN XY:

133466

show subpopulations

Gnomad AFR exome

AF:

0.0000653

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000653

Gnomad NFE exome

AF:

0.000350

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000430

AC:

628

AN:

1460142

Hom.:

Cov.:

AF XY:

0.000421

AC XY:

306

AN XY:

726114

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000637

Gnomad4 NFE exome

AF:

0.000511

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000282

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000277

AC:

ESP6500EA

AF:

0.000368

AC:

ExAC

AF:

0.000141

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

Dec 03, 2024

The c.788A>C (p.E263A) alteration is located in exon 3 (coding exon 3) of the ZC3H12C gene. This alteration results from a A to C substitution at nucleotide position 788, causing the glutamic acid (E) at amino acid position 263 to be replaced by an alanine (A). 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

0.94

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.;T

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.58

D;D;D

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.7

M;.;.

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-5.5

D;D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.80

MVP

0.10

MPC

0.037

ClinPred

0.49

GERP RS

5.9

Varity_R

0.74

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.25

Position offset: -14

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