1-100352908-T-C

Position:

• chr1-100352908-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003672.4(CDC14A):​c.-47T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 1,612,912 control chromosomes in the GnomAD database, including 773,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73541 hom., cov: 33)
  • Exomes 𝑓: 0.98 (700034 hom.)
• Consequence: CDC14A NM_003672.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.623

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 1-100352908-T-C is Benign according to our data. Variant chr1-100352908-T-C is described in ClinVar as [Benign]. Clinvar id is 1192711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC14A	NM_003672.4	c.-47T>C		5_prime_UTR_variant	1/16	ENST00000336454.5	NP_003663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC14A	ENST00000336454.5	c.-47T>C		5_prime_UTR_variant	1/16	1	NM_003672.4	ENSP00000336739.3

Frequencies

GnomAD3 genomes AF: 0.983 AC: 149546 AN: 152198 Hom.: 73482 Cov.: 33

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.978

Gnomad OTH AF: 0.985

GnomAD3 exomes AF: 0.978 AC: 243212 AN: 248668 Hom.: 118950 AF XY: 0.978 AC XY: 131615 AN XY: 134634

Gnomad AFR exome AF: 0.996

Gnomad AMR exome AF: 0.966

Gnomad ASJ exome AF: 0.998

Gnomad EAS exome AF: 0.984

Gnomad SAS exome AF: 0.969

Gnomad FIN exome AF: 0.974

Gnomad NFE exome AF: 0.979

Gnomad OTH exome AF: 0.980

GnomAD4 exome AF: 0.979 AC: 1429954 AN: 1460596 Hom.: 700034 Cov.: 51 AF XY: 0.979 AC XY: 711256 AN XY: 726566

Gnomad4 AFR exome AF: 0.997

Gnomad4 AMR exome AF: 0.967

Gnomad4 ASJ exome AF: 0.997

Gnomad4 EAS exome AF: 0.986

Gnomad4 SAS exome AF: 0.970

Gnomad4 FIN exome AF: 0.975

Gnomad4 NFE exome AF: 0.979

Gnomad4 OTH exome AF: 0.983

GnomAD4 genome AF: 0.983 AC: 149665 AN: 152316 Hom.: 73541 Cov.: 33 AF XY: 0.982 AC XY: 73112 AN XY: 74472

Gnomad4 AFR AF: 0.995

Gnomad4 AMR AF: 0.970

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.972

Gnomad4 FIN AF: 0.973

Gnomad4 NFE AF: 0.979

Gnomad4 OTH AF: 0.985

Alfa AF: 0.985 Hom.: 14988

Bravo AF: 0.984

Asia WGS AF: 0.979 AC: 3405 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Autosomal recessive nonsyndromic hearing loss 32 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs594529; hg19: chr1-100818464;