15-90970444-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/20 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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.585

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRC1	NM_003981.4	c.1532A>G	p.Tyr511Cys	missense_variant	12/15	ENST00000394249.8
PRC1-AS1	NR_051984.1	n.310+3766T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRC1	ENST00000394249.8	c.1532A>G	p.Tyr511Cys	missense_variant	12/15	1	NM_003981.4
PRC1-AS1	ENST00000554388.2	n.339+3766T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0518 AC: 7872 AN: 152078 Hom.: 296 Cov.: 31

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

GnomAD3 exomes AF: 0.0646 AC: 16228 AN: 251372 Hom.: 807 AF XY: 0.0710 AC XY: 9640 AN XY: 135868

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 SAS exome AF: 0.155

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.: 31 AF XY: 0.0718 AC XY: 52214 AN XY: 726746

Gnomad4 AFR exome AF: 0.00992

Gnomad4 AMR exome AF: 0.0274

Gnomad4 ASJ exome AF: 0.0716

Gnomad4 EAS exome AF: 0.00197

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.0692

Gnomad4 NFE exome AF: 0.0689

Gnomad4 OTH exome AF: 0.0667

GnomAD4 genome AF: 0.0517 AC: 7864 AN: 152196 Hom.: 293 Cov.: 31 AF XY: 0.0519 AC XY: 3865 AN XY: 74410

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0724

Gnomad4 NFE AF: 0.0712

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0675 Hom.: 771

Bravo AF: 0.0453

TwinsUK AF: 0.0715 AC: 265

ALSPAC AF: 0.0711 AC: 274

ESP6500AA AF: 0.0152 AC: 67

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial cancer of breast Uncertain:1

Uncertain significance, no assertion criteria provided

research

Research Lab, National Institute of Public Health

Feb 01, 2014

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	9.3
Dann	Benign	0.51
DEOGEN2	Benign	0.053	T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.94	D;D;D
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.40	N;N;.
MutationTaster	Benign	0.63	D;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.53	N;N;N
REVEL	Benign	0.055
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.042
MPC		0.093
ClinPred		0.0054	T
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs12911192; hg19: chr15-91513674; COSMIC: COSV62695337; COSMIC: COSV62695337;