11-110125219-C-T

Variant names:

• chr11-110125219-C-T
• rs746463
• NM_033390.2:c.22-11444C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033390.2(ZC3H12C):​c.22-11444C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 151,450 control chromosomes in the GnomAD database, including 38,413 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (38413 hom., cov: 29)
• Consequence: ZC3H12C NM_033390.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• Publications: 23 publications found

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]

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 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 24

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033390.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H12C	NM_033390.2	MANE Select	c.22-11444C>T		intron	N/A	NP_203748.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H12C	ENST00000278590.8	TSL:2 MANE Select	c.22-11444C>T		intron	N/A	ENSP00000278590.3
	RDX	ENST00000645527.1		n.*546-949G>A		intron	N/A	ENSP00000496121.1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107431 AN: 151334 Hom.: 38403 Cov.: 29

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.698

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.710 AC: 107491 AN: 151450 Hom.: 38413 Cov.: 29 AF XY: 0.704 AC XY: 52065 AN XY: 73904

African (AFR) AF: 0.758 AC: 31284 AN: 41280

American (AMR) AF: 0.731 AC: 11146 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2369 AN: 3464

East Asian (EAS) AF: 0.892 AC: 4592 AN: 5150

South Asian (SAS) AF: 0.581 AC: 2783 AN: 4790

European-Finnish (FIN) AF: 0.585 AC: 6038 AN: 10324

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.693 AC: 47025 AN: 67888

Other (OTH) AF: 0.698 AC: 1472 AN: 2108

Alfa AF: 0.705 Hom.: 69563

Bravo AF: 0.724

Asia WGS AF: 0.715 AC: 2482 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.22
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs746463; hg19: chr11-109995944;