NM_003981.4:c.1532A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003981.4(PRC1):c.1532A>G(p.Tyr511Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 1,613,012 control chromosomes in the GnomAD database, including 4,426 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.052 ( 293 hom., cov: 31)

Exomes 𝑓: 0.069 ( 4133 hom. )

Consequence

PRC1
NM_003981.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.585

Publications

36 publications found

Variant links:

Genes affected

PRC1 (HGNC:9341): (protein regulator of cytokinesis 1) This gene encodes a protein that is involved in cytokinesis. The protein is present at high levels during the S and G2/M phases of mitosis but its levels drop dramatically when the cell exits mitosis and enters the G1 phase. It is located in the nucleus during interphase, becomes associated with mitotic spindles in a highly dynamic manner during mitosis, and localizes to the cell mid-body during cytokinesis. This protein has been shown to be a substrate of several cyclin-dependent kinases (CDKs). It is necessary for polarizing parallel microtubules and concentrating the factors responsible for contractile ring assembly. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

PRC1 links:

ENSG00000284946 (HGNC:):

ENSG00000284946 links:

PRC1-AS1 (HGNC:48587): (PRC1 antisense RNA 1)

PRC1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0016720891).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003981.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRC1	NM_003981.4	MANE Select	c.1532A>G	p.Tyr511Cys	missense	Exon 12 of 15	NP_003972.2	O43663-1
PRC1	NM_199413.3		c.1532A>G	p.Tyr511Cys	missense	Exon 12 of 14	NP_955445.2	O43663-4
PRC1	NM_001267580.2		c.1409A>G	p.Tyr470Cys	missense	Exon 11 of 13	NP_001254509.2	O43663-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRC1	ENST00000394249.8	TSL:1 MANE Select	c.1532A>G	p.Tyr511Cys	missense	Exon 12 of 15	ENSP00000377793.3	O43663-1
PRC1	ENST00000361188.9	TSL:1	c.1532A>G	p.Tyr511Cys	missense	Exon 12 of 14	ENSP00000354679.5	O43663-4
ENSG00000284946	ENST00000643536.1		n.*1495A>G		non_coding_transcript_exon	Exon 33 of 35	ENSP00000494429.1	A0A2R8YDQ0

Frequencies

GnomAD3 genomes

AF:

0.0518

AC:

7872

AN:

152078

Hom.:

296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0375

Gnomad ASJ

AF:

0.0764

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.0724

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0712

Gnomad OTH

AF:

0.0532

GnomAD2 exomes

AF:

0.0646

AC:

16228

AN:

251372

AF XY:

0.0710

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.0252

Gnomad ASJ exome

AF:

0.0751

Gnomad EAS exome

AF:

0.00190

Gnomad FIN exome

AF:

0.0705

Gnomad NFE exome

AF:

0.0680

Gnomad OTH exome

AF:

0.0648

GnomAD4 exome

AF:

0.0692

AC:

101055

AN:

1460816

Hom.:

4133

Cov.:

AF XY:

0.0718

AC XY:

52214

AN XY:

726746

show subpopulations

African (AFR)

AF:

0.00992

AC:

332

AN:

33470

American (AMR)

AF:

0.0274

AC:

1224

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0716

AC:

1872

AN:

26128

East Asian (EAS)

AF:

0.00197

AC:

AN:

39692

South Asian (SAS)

AF:

0.151

AC:

12997

AN:

86200

European-Finnish (FIN)

AF:

0.0692

AC:

3697

AN:

53406

Middle Eastern (MID)

AF:

0.0572

AC:

330

AN:

5766

European-Non Finnish (NFE)

AF:

0.0689

AC:

76503

AN:

1111094

Other (OTH)

AF:

0.0667

AC:

4022

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

4578

9157

13735

18314

22892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2846

5692

8538

11384

14230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0517

AC:

7864

AN:

152196

Hom.:

293

Cov.:

AF XY:

0.0519

AC XY:

3865

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0113

AC:

469

AN:

41542

American (AMR)

AF:

0.0374

AC:

572

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0764

AC:

265

AN:

3468

East Asian (EAS)

AF:

0.00328

AC:

AN:

5184

South Asian (SAS)

AF:

0.145

AC:

700

AN:

4820

European-Finnish (FIN)

AF:

0.0724

AC:

767

AN:

10598

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0712

AC:

4839

AN:

67992

Other (OTH)

AF:

0.0526

AC:

111

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

386

773

1159

1546

1932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0653

Hom.:

1069

Bravo

AF:

0.0453

TwinsUK

AF:

0.0715

AC:

265

ALSPAC

AF:

0.0711

AC:

274

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.0735

AC:

632

ExAC

AF:

0.0658

AC:

7989

Asia WGS

AF:

0.0790

AC:

275

AN:

3478

EpiCase

AF:

0.0749

EpiControl

AF:

0.0675

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial cancer of breast (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.3

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.053

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.40

PhyloP100

0.58

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.53

REVEL

Benign

0.055

Sift

Benign

0.13

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.042

MPC

0.093

ClinPred

0.0054

GERP RS

-1.8

PromoterAI

0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.41

Mutation Taster

=80/20

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over