rs10875295

Variant names:

• chr1-100504790-T-C
• rs10875295
• NM_003672.4:c.1755+5528T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-100504790-T-C
• chr1-100504790-T-G

Variant summary

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

The NM_003672.4(CDC14A):​c.1755+5528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,519,584 control chromosomes in the GnomAD database, including 177,197 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 0.50 (19434 hom., cov: 31)
  • Exomes 𝑓: 0.48 (157763 hom.)
• Consequence: CDC14A NM_003672.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC14A	NM_003672.4	MANE Select	c.1755+5528T>C		intron	N/A	NP_003663.2
	CDC14A	NM_001319210.2		c.1756-24T>C		intron	N/A	NP_001306139.1	Q9UNH5-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC14A	ENST00000336454.5	TSL:1 MANE Select	c.1755+5528T>C		intron	N/A	ENSP00000336739.3	Q9UNH5-1
	CDC14A	ENST00000644813.1		c.1756-24T>C		intron	N/A	ENSP00000496374.1	Q9UNH5-5
	CDC14A	ENST00000873832.1		c.1800+5528T>C		intron	N/A	ENSP00000543891.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75825 AN: 151852 Hom.: 19416 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.482

GnomAD2 exomes AF: 0.460 AC: 61679 AN: 134230 AF XY: 0.456

Gnomad AFR exome AF: 0.625

Gnomad AMR exome AF: 0.422

Gnomad ASJ exome AF: 0.494

Gnomad EAS exome AF: 0.465

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.480

Gnomad OTH exome AF: 0.457

GnomAD4 exome AF: 0.479 AC: 654583 AN: 1367612 Hom.: 157763 Cov.: 26 AF XY: 0.476 AC XY: 321469 AN XY: 675896

African (AFR) AF: 0.619 AC: 19298 AN: 31190

American (AMR) AF: 0.418 AC: 14919 AN: 35662

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 12558 AN: 25066

East Asian (EAS) AF: 0.500 AC: 17813 AN: 35616

South Asian (SAS) AF: 0.405 AC: 31945 AN: 78892

European-Finnish (FIN) AF: 0.406 AC: 13744 AN: 33860

Middle Eastern (MID) AF: 0.472 AC: 2669 AN: 5660

European-Non Finnish (NFE) AF: 0.483 AC: 513702 AN: 1064332

Other (OTH) AF: 0.487 AC: 27935 AN: 57334

GnomAD4 genome AF: 0.499 AC: 75883 AN: 151972 Hom.: 19434 Cov.: 31 AF XY: 0.492 AC XY: 36540 AN XY: 74298

African (AFR) AF: 0.612 AC: 25344 AN: 41440

American (AMR) AF: 0.426 AC: 6516 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3466

East Asian (EAS) AF: 0.488 AC: 2526 AN: 5174

South Asian (SAS) AF: 0.405 AC: 1951 AN: 4812

European-Finnish (FIN) AF: 0.396 AC: 4185 AN: 10558

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 31972 AN: 67938

Other (OTH) AF: 0.487 AC: 1022 AN: 2100

Alfa AF: 0.480 Hom.: 31339

Bravo AF: 0.508

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.83
PhyloP100		-0.82
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: rs10875295; hg19: chr1-100970346; COSMIC: COSV60556263;