chr1-193142098-T-TGA

Position:

• chr1-193142098-T-TGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.164

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]

ACMG classification

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	c.729+50_729+51dup		intron_variant		ENST00000367435.5	NP_078805.3
CDC73	XM_006711537.5	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	c.729+50_729+51dup		intron_variant		1	NM_024529.5	ENSP00000356405	P1

Frequencies

GnomAD3 genomes AF: 0.000639 AC: 95 AN: 148720 Hom.: 0 Cov.: 32

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.: 1 Cov.: 0 AF XY: 0.000963 AC XY: 623 AN XY: 646642

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: 95 AN: 148800 Hom.: 0 Cov.: 32 AF XY: 0.000731 AC XY: 53 AN XY: 72522

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

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs80356646; hg19: chr1-193111228;