Variant 11-110137176-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033390.2(ZC3H12C):c.535G>A(p.Val179Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,538 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: 7.75

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15226012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H12C	NM_033390.2 link	c.535G>A	p.Val179Ile	missense_variant	2/6	ENST00000278590.8	NP_203748.1	Q9C0D7-1
ZC3H12C	NM_001411037.1 link	c.538G>A	p.Val180Ile	missense_variant	2/6		NP_001397966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZC3H12C	ENST00000278590.8 link	c.535G>A	p.Val179Ile	missense_variant	2/6	2	NM_033390.2	ENSP00000278590.3	Q9C0D7-1
ZC3H12C	ENST00000528673.5 link	c.538G>A	p.Val180Ile	missense_variant	2/6	2		ENSP00000431821.1	Q9C0D7-2
ZC3H12C	ENST00000453089.2 link	c.442G>A	p.Val148Ile	missense_variant	1/5	2		ENSP00000413094.2	E9PP00
RDX	ENST00000645527.1 link	n.*251-5446C>T		intron_variant				ENSP00000496121.1	A0A2R8Y7M3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461538

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

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 10, 2024

The c.535G>A (p.V179I) alteration is located in exon 2 (coding exon 2) of the ZC3H12C gene. This alteration results from a G to A substitution at nucleotide position 535, causing the valine (V) at amino acid position 179 to be replaced by an isoleucine (I). 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

0.22

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

T;.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.5

L;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.090

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.57

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.99

D;.;.

Vest4

0.29

MutPred

0.33

Loss of disorder (P = 0.303);.;.;

MVP

0.14

MPC

0.032

ClinPred

0.89

GERP RS

4.5

Varity_R

0.084

gMVP

0.38

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over