rs7543221

Variant names:

• chr1-100462868-C-T
• rs7543221
• NM_003672.4:c.825C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-100462868-C-T
• chr1-100462868-C-A
• chr1-100462868-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001319212.2(CDC14A):​c.-55C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,466 control chromosomes in the GnomAD database, including 1,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (834 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (704 hom.)
• Consequence: CDC14A NM_001319212.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.645
• Publications: 4 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):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic deafness 105

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hearing impairment and infertile male syndrome

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive nonsyndromic hearing loss 32

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000228086 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 1-100462868-C-T is Benign according to our data. Variant chr1-100462868-C-T is described in ClinVar as Benign. ClinVar VariationId is 517533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319212.2. 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
	CDC14A	NM_003672.4	MANE Select	c.825C>T	p.Ala275Ala	synonymous	Exon 9 of 16	NP_003663.2
	CDC14A	NM_001319212.2		c.-55C>T		5_prime_UTR_premature_start_codon_gain	Exon 8 of 14	NP_001306141.1
	CDC14A	NM_033312.3		c.825C>T	p.Ala275Ala	synonymous	Exon 9 of 15	NP_201569.1	Q9UNH5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC14A	ENST00000336454.5	TSL:1 MANE Select	c.825C>T	p.Ala275Ala	synonymous	Exon 9 of 16	ENSP00000336739.3	Q9UNH5-1
	CDC14A	ENST00000361544.11	TSL:1	c.825C>T	p.Ala275Ala	synonymous	Exon 9 of 15	ENSP00000354916.6	Q9UNH5-2
	CDC14A	ENST00000370124.8	TSL:1	c.825C>T	p.Ala275Ala	synonymous	Exon 9 of 11	ENSP00000359142.3	Q9UNH5-3

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8548 AN: 151920 Hom.: 829 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000834

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.0393

GnomAD2 exomes AF: 0.0154 AC: 3861 AN: 250904 AF XY: 0.0111

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.00940

Gnomad ASJ exome AF: 0.00695

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000829

Gnomad OTH exome AF: 0.00768

GnomAD4 exome AF: 0.00598 AC: 8742 AN: 1461428 Hom.: 704 Cov.: 30 AF XY: 0.00521 AC XY: 3790 AN XY: 727032

African (AFR) AF: 0.200 AC: 6681 AN: 33450

American (AMR) AF: 0.0109 AC: 489 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00524 AC: 137 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39656

South Asian (SAS) AF: 0.000638 AC: 55 AN: 86206

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53408

Middle Eastern (MID) AF: 0.0130 AC: 75 AN: 5764

European-Non Finnish (NFE) AF: 0.000451 AC: 501 AN: 1111722

Other (OTH) AF: 0.0132 AC: 799 AN: 60378

GnomAD4 genome AF: 0.0564 AC: 8579 AN: 152038 Hom.: 834 Cov.: 32 AF XY: 0.0545 AC XY: 4052 AN XY: 74302

African (AFR) AF: 0.196 AC: 8129 AN: 41440

American (AMR) AF: 0.0191 AC: 292 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000626 AC: 3 AN: 4794

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10590

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000662 AC: 45 AN: 67980

Other (OTH) AF: 0.0389 AC: 82 AN: 2110

Alfa AF: 0.0230 Hom.: 857

Bravo AF: 0.0633

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.00124

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	4.2
DANN	Benign	0.92
PhyloP100		-0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=88/12	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: rs7543221; hg19: chr1-100928424;