rs508020

Variant names:

• chr1-100489976-T-C
• rs508020
• NM_003672.4:c.1138-4842T>C

Variant summary

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

The NM_033312.3(CDC14A):​c.1138-4842T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,028 control chromosomes in the GnomAD database, including 13,592 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 0.41 (13592 hom., cov: 31)
• Consequence: CDC14A NM_033312.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 10 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

ENSG00000228086 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033312.3. 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
	CDC14A	NM_003672.4	MANE Select	c.1138-4842T>C		intron	N/A	NP_003663.2
	CDC14A	NM_033312.3		c.1138-4842T>C		intron	N/A	NP_201569.1
	CDC14A	NM_001319210.2		c.1138-4842T>C		intron	N/A	NP_001306139.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC14A	ENST00000336454.5	TSL:1 MANE Select	c.1138-4842T>C		intron	N/A	ENSP00000336739.3
	CDC14A	ENST00000361544.11	TSL:1	c.1138-4842T>C		intron	N/A	ENSP00000354916.6
	CDC14A	ENST00000644676.1		c.1141-4842T>C		intron	N/A	ENSP00000494661.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62735 AN: 151910 Hom.: 13595 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.413 AC: 62743 AN: 152028 Hom.: 13592 Cov.: 31 AF XY: 0.412 AC XY: 30609 AN XY: 74356

African (AFR) AF: 0.288 AC: 11936 AN: 41444

American (AMR) AF: 0.398 AC: 6089 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3466

East Asian (EAS) AF: 0.372 AC: 1917 AN: 5160

South Asian (SAS) AF: 0.484 AC: 2329 AN: 4812

European-Finnish (FIN) AF: 0.472 AC: 4993 AN: 10574

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32499 AN: 67974

Other (OTH) AF: 0.427 AC: 900 AN: 2106

Alfa AF: 0.450 Hom.: 43360

Bravo AF: 0.401

Asia WGS AF: 0.415 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.74
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: rs508020; hg19: chr1-100955532;