Variant 1-193142098-TGAGAGAGA-TGAGAGAGAGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000367435.5(CDC73):c.729+50_729+51dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000913 in 1,434,650 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 1 hom. )

Consequence

CDC73
ENST00000367435.5 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.164

Variant links:

Genes affected

CDC73 (HGNC:16783): (cell division cycle 73) This gene encodes a tumor suppressor that is involved in transcriptional and post-transcriptional control pathways. The protein is a component of the the PAF protein complex, which associates with the RNA polymerase II subunit POLR2A and with a histone methyltransferase complex. This protein appears to facilitate the association of 3' mRNA processing factors with actively-transcribed chromatin. Mutations in this gene have been linked to hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism, and parathyroid carcinoma. [provided by RefSeq, Jul 2009]

CDC73 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 1-193142098-T-TGA is Benign according to our data. Variant chr1-193142098-T-TGA is described in ClinVar as [Likely_benign]. Clinvar id is 2692168.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000638 (95/148800) while in subpopulation AMR AF= 0.00087 (13/14944). AF 95% confidence interval is 0.000636. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 95 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC73	NM_024529.5 linkuse as main transcript	c.729+50_729+51dup		intron_variant		ENST00000367435.5	NP_078805.3
CDC73	XM_006711537.5 linkuse as main transcript	c.729+50_729+51dup		intron_variant			XP_006711600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC73	ENST00000367435.5 linkuse as main transcript	c.729+50_729+51dup		intron_variant		1	NM_024529.5	ENSP00000356405	P1

Frequencies

GnomAD3 genomes

AF:

0.000639

AC:

AN:

148720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000862

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000871

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000585

Gnomad SAS

AF:

0.000637

Gnomad FIN

AF:

0.000307

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000553

Gnomad OTH

AF:

0.000490

GnomAD4 exome

AF:

0.000945

AC:

1215

AN:

1285850

Hom.:

Cov.:

AF XY:

0.000963

AC XY:

623

AN XY:

646642

show subpopulations

Gnomad4 AFR exome

AF:

0.000944

Gnomad4 AMR exome

AF:

0.000641

Gnomad4 ASJ exome

AF:

0.000365

Gnomad4 EAS exome

AF:

0.000771

Gnomad4 SAS exome

AF:

0.000467

Gnomad4 FIN exome

AF:

0.000271

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.000638

AC:

AN:

148800

Hom.:

Cov.:

AF XY:

0.000731

AC XY:

AN XY:

72522

show subpopulations

Gnomad4 AFR

AF:

0.000860

Gnomad4 AMR

AF:

0.000870

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000586

Gnomad4 SAS

AF:

0.000639

Gnomad4 FIN

AF:

0.000307

Gnomad4 NFE

AF:

0.000553

Gnomad4 OTH

AF:

0.000486

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Feb 06, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over