chr1-193181743-T-C

Variant names:

• chr1-193181743-T-C
• rs10494675
• NM_024529.5:c.973-22052T>C

Variant summary

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

The NM_024529.5(CDC73):​c.973-22052T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 559,820 control chromosomes in the GnomAD database, including 523 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 0.046 (159 hom., cov: 32)
  • Exomes 𝑓: 0.040 (364 hom.)
• Consequence: CDC73 NM_024529.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 9 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]

B3GALT2 (HGNC:917): (beta-1,3-galactosyltransferase 2) This gene is a member of the beta-1,3-galactosyltransferase (beta3GalT) gene family. This family encodes type II membrane-bound glycoproteins with diverse enzymatic functions using different donor substrates (UDP-galactose and UDP-N-acetylglucosamine) and different acceptor sugars (N-acetylglucosamine, galactose, N-acetylgalactosamine). The beta3GalT genes are distantly related to the Drosophila Brainiac gene and have the protein coding sequence contained in a single exon. The beta3GalT proteins also contain conserved sequences not found in the beta4GalT or alpha3GalT proteins. The carbohydrate chains synthesized by these enzymes are designated as type 1, whereas beta4GalT enzymes synthesize type 2 carbohydrate chains. The ratio of type 1:type 2 chains changes during embryogenesis. By sequence similarity, the beta3GalT genes fall into at least two groups: beta3GalT4 and 4 other beta3GalT genes (beta3GalT1-3, beta3GalT5). This gene encodes a protein that functions in N-linked glycoprotein glycosylation and shows strict donor substrate specificity for UDP-galactose. [provided by RefSeq, Jul 2008]

ENSG00000308280 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0562 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC73	NM_024529.5	MANE Select	c.973-22052T>C		intron	N/A	NP_078805.3
	B3GALT2	NM_003783.3	MANE Select	c.-120-61A>G		intron	N/A	NP_003774.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC73	ENST00000367435.5	TSL:1 MANE Select	c.973-22052T>C		intron	N/A	ENSP00000356405.4
	B3GALT2	ENST00000367434.5	TSL:1 MANE Select	c.-120-61A>G		intron	N/A	ENSP00000356404.4
	CDC73	ENST00000635846.1	TSL:5	c.730-22052T>C		intron	N/A	ENSP00000490035.1

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6933 AN: 152160 Hom.: 157 Cov.: 32

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0390

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0449

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0489

GnomAD4 exome AF: 0.0398 AC: 16222 AN: 407542 Hom.: 364 AF XY: 0.0391 AC XY: 8237 AN XY: 210726

African (AFR) AF: 0.0574 AC: 604 AN: 10524

American (AMR) AF: 0.0338 AC: 425 AN: 12556

Ashkenazi Jewish (ASJ) AF: 0.0485 AC: 610 AN: 12590

East Asian (EAS) AF: 0.000107 AC: 3 AN: 28126

South Asian (SAS) AF: 0.0149 AC: 415 AN: 27832

European-Finnish (FIN) AF: 0.0420 AC: 1469 AN: 34978

Middle Eastern (MID) AF: 0.0486 AC: 89 AN: 1832

European-Non Finnish (NFE) AF: 0.0454 AC: 11582 AN: 255272

Other (OTH) AF: 0.0430 AC: 1025 AN: 23832

GnomAD4 genome AF: 0.0456 AC: 6951 AN: 152278 Hom.: 159 Cov.: 32 AF XY: 0.0455 AC XY: 3388 AN XY: 74458

African (AFR) AF: 0.0581 AC: 2414 AN: 41562

American (AMR) AF: 0.0389 AC: 595 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 184 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0156 AC: 75 AN: 4820

European-Finnish (FIN) AF: 0.0449 AC: 477 AN: 10616

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0452 AC: 3077 AN: 68018

Other (OTH) AF: 0.0479 AC: 101 AN: 2110

Alfa AF: 0.0467 Hom.: 253

Bravo AF: 0.0464

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.68
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

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: rs10494675; hg19: chr1-193150873;