11-110124562-C-T

Variant names:

• chr11-110124562-C-T
• rs1789369
• NM_033390.2:c.22-12101C>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.22-12101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,092 control chromosomes in the GnomAD database, including 38,496 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 (38496 hom., cov: 32)
• Consequence: ZC3H12C NM_033390.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.633
• Publications: 13 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.93).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H12C	NM_033390.2	MANE Select	c.22-12101C>T		intron	N/A	NP_203748.1	Q9C0D7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H12C	ENST00000278590.8	TSL:2 MANE Select	c.22-12101C>T		intron	N/A	ENSP00000278590.3	Q9C0D7-1
	RDX	ENST00000645527.1		n.*546-292G>A		intron	N/A	ENSP00000496121.1	A0A2R8Y7M3

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107725 AN: 151974 Hom.: 38486 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.709 AC: 107785 AN: 152092 Hom.: 38496 Cov.: 32 AF XY: 0.703 AC XY: 52243 AN XY: 74338

African (AFR) AF: 0.757 AC: 31428 AN: 41498

American (AMR) AF: 0.730 AC: 11169 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3470

East Asian (EAS) AF: 0.892 AC: 4620 AN: 5180

South Asian (SAS) AF: 0.580 AC: 2798 AN: 4822

European-Finnish (FIN) AF: 0.578 AC: 6089 AN: 10532

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47056 AN: 67984

Other (OTH) AF: 0.697 AC: 1474 AN: 2114

Alfa AF: 0.699 Hom.: 156822

Bravo AF: 0.724

Asia WGS AF: 0.715 AC: 2484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.48
PhyloP100		-0.63
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: rs1789369; hg19: chr11-109995287;