chr1-193125238-TTATC-T

Variant names:

• chr1-193125238-TTATC-T
• rs80356645
• NM_024529.5:c.237+29_237+32delCTAT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_024529.5(CDC73):​c.237+29_237+32delCTAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 1,331,598 control chromosomes in the GnomAD database, including 5,691 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (734 hom., cov: 32)
  • Exomes 𝑓: 0.047 (4957 hom.)
• Consequence: CDC73 NM_024529.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.263
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• hyperparathyroidism 2 with jaw tumors

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen
• hyperparathyroidism 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• parathyroid gland carcinoma

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial isolated hyperparathyroidism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000308280 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-193125238-TTATC-T is Benign according to our data. Variant chr1-193125238-TTATC-T is described in ClinVar as Benign. ClinVar VariationId is 21684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024529.5. 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
	CDC73	NM_024529.5	MANE Select	c.237+29_237+32delCTAT		intron	N/A	NP_078805.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC73	ENST00000367435.5	TSL:1 MANE Select	c.237+22_237+25delTATC		intron	N/A	ENSP00000356405.4	Q6P1J9
	CDC73	ENST00000958309.1		c.237+22_237+25delTATC		intron	N/A	ENSP00000628368.1
	CDC73	ENST00000958310.1		c.237+22_237+25delTATC		intron	N/A	ENSP00000628369.1

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7209 AN: 152160 Hom.: 735 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0702

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.0821

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0468

GnomAD2 exomes AF: 0.0830 AC: 20784 AN: 250312 AF XY: 0.0794

Gnomad AFR exome AF: 0.00947

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.0325

Gnomad EAS exome AF: 0.492

Gnomad FIN exome AF: 0.0601

Gnomad NFE exome AF: 0.0291

Gnomad OTH exome AF: 0.0602

GnomAD4 exome AF: 0.0474 AC: 55937 AN: 1179320 Hom.: 4957 AF XY: 0.0483 AC XY: 29022 AN XY: 601002

African (AFR) AF: 0.00723 AC: 202 AN: 27920

American (AMR) AF: 0.122 AC: 5406 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.0318 AC: 777 AN: 24426

East Asian (EAS) AF: 0.438 AC: 16637 AN: 37998

South Asian (SAS) AF: 0.0685 AC: 5509 AN: 80384

European-Finnish (FIN) AF: 0.0553 AC: 2944 AN: 53236

Middle Eastern (MID) AF: 0.0422 AC: 220 AN: 5210

European-Non Finnish (NFE) AF: 0.0250 AC: 21387 AN: 854718

Other (OTH) AF: 0.0559 AC: 2855 AN: 51104

GnomAD4 genome AF: 0.0473 AC: 7200 AN: 152278 Hom.: 734 Cov.: 32 AF XY: 0.0520 AC XY: 3871 AN XY: 74458

African (AFR) AF: 0.0104 AC: 432 AN: 41576

American (AMR) AF: 0.0704 AC: 1078 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.481 AC: 2479 AN: 5152

South Asian (SAS) AF: 0.0815 AC: 393 AN: 4822

European-Finnish (FIN) AF: 0.0588 AC: 624 AN: 10610

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0290 AC: 1973 AN: 68022

Other (OTH) AF: 0.0459 AC: 97 AN: 2114

Alfa AF: 0.0380 Hom.: 41

Bravo AF: 0.0507

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.26
Mutation Taster		=100/0	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: rs80356645; hg19: chr1-193094368;