rs12096135

Variant names:

• chr1-100385746-G-A
• rs12096135
• NM_003672.4:c.217-4986G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-100385746-G-A
• chr1-100385746-G-C

Variant summary

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

The NM_003672.4(CDC14A):​c.217-4986G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,082 control chromosomes in the GnomAD database, including 1,504 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 0.13 (1504 hom., cov: 32)
• Consequence: CDC14A NM_003672.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 1 publications found

Genes affected

CDC14A (HGNC:1718): (cell division cycle 14A) The protein encoded by this gene is a member of the dual specificity protein tyrosine phosphatase family. It is highly similar to Saccharomyces cerevisiae Cdc14, a protein tyrosine phosphatase involved in the exit of cell mitosis and initiation of DNA replication, suggesting a role in cell cycle control. This protein has been shown to interact with, and dephosphorylate tumor suppressor protein p53, and is thought to regulate the function of p53. Alternative splicing of this gene results in several transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

CDC14A Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic deafness 105

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive nonsyndromic hearing loss 32

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia
• hearing impairment and infertile male syndrome

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003672.4. 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
	CDC14A	NM_003672.4	MANE Select	c.217-4986G>A		intron	N/A	NP_003663.2
	CDC14A	NM_033312.3		c.217-4986G>A		intron	N/A	NP_201569.1
	CDC14A	NM_001319210.2		c.217-4986G>A		intron	N/A	NP_001306139.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC14A	ENST00000336454.5	TSL:1 MANE Select	c.217-4986G>A		intron	N/A	ENSP00000336739.3
	CDC14A	ENST00000361544.11	TSL:1	c.217-4986G>A		intron	N/A	ENSP00000354916.6
	CDC14A	ENST00000370124.8	TSL:1	c.217-4986G>A		intron	N/A	ENSP00000359142.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19841 AN: 151964 Hom.: 1505 Cov.: 32

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0993

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.0839

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.130 AC: 19841 AN: 152082 Hom.: 1504 Cov.: 32 AF XY: 0.131 AC XY: 9717 AN XY: 74340

African (AFR) AF: 0.0838 AC: 3474 AN: 41480

American (AMR) AF: 0.0992 AC: 1515 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3468

East Asian (EAS) AF: 0.0541 AC: 280 AN: 5180

South Asian (SAS) AF: 0.0831 AC: 401 AN: 4826

European-Finnish (FIN) AF: 0.211 AC: 2231 AN: 10564

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10932 AN: 67972

Other (OTH) AF: 0.119 AC: 251 AN: 2108

Alfa AF: 0.149 Hom.: 345

Bravo AF: 0.120

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.62
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12096135; hg19: chr1-100851302;