rs12911192

Variant names:

• chr15-90970444-T-C
• rs12911192
• NM_003981.4:c.1532A>G

Variant summary

Our verdict is Benign. The variant received -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. 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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.585
• Publications: 36 publications found

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]

ENSG00000284946 (HGNC:):

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

ACMG classification

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

Sel.	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

Sel.	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.: 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

GnomAD2 exomes AF: 0.0646 AC: 16228 AN: 251372 AF XY: 0.0710

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

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: 78 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

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

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: 17 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: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0712 AC: 4839 AN: 67992

Other (OTH) AF: 0.0526 AC: 111 AN: 2110

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: 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

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	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	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
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.40	N
PhyloP100		0.58
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.055
Sift	Benign	0.13	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.042
MPC		0.093
ClinPred		0.0054	T
GERP RS		-1.8
PromoterAI		0.024	Neutral
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)

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

Other links and lift over

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