rs10494675

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000367435.5(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
ENST00000367435.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.74
Variant links:
Genes affected
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
B3GALT2NM_003783.3 linkuse as main transcriptc.-120-61A>G intron_variant ENST00000367434.5 NP_003774.1
CDC73NM_024529.5 linkuse as main transcriptc.973-22052T>C intron_variant ENST00000367435.5 NP_078805.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
B3GALT2ENST00000367434.5 linkuse as main transcriptc.-120-61A>G intron_variant 1 NM_003783.3 ENSP00000356404 P1
CDC73ENST00000367435.5 linkuse as main transcriptc.973-22052T>C intron_variant 1 NM_024529.5 ENSP00000356405 P1

Frequencies

GnomAD3 genomes
AF:
0.0456
AC:
6933
AN:
152160
Hom.:
157
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0574
Gnomad4 AMR exome
AF:
0.0338
Gnomad4 ASJ exome
AF:
0.0485
Gnomad4 EAS exome
AF:
0.000107
Gnomad4 SAS exome
AF:
0.0149
Gnomad4 FIN exome
AF:
0.0420
Gnomad4 NFE exome
AF:
0.0454
Gnomad4 OTH exome
AF:
0.0430
GnomAD4 genome
AF:
0.0456
AC:
6951
AN:
152278
Hom.:
159
Cov.:
32
AF XY:
0.0455
AC XY:
3388
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0581
Gnomad4 AMR
AF:
0.0389
Gnomad4 ASJ
AF:
0.0531
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.0156
Gnomad4 FIN
AF:
0.0449
Gnomad4 NFE
AF:
0.0452
Gnomad4 OTH
AF:
0.0479
Alfa
AF:
0.0468
Hom.:
193
Bravo
AF:
0.0464
Asia WGS
AF:
0.0140
AC:
48
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
6.5
DANN
Benign
0.68

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

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

Other links and lift over

dbSNP: rs10494675; hg19: chr1-193150873; API