rs200964554

Variant names:

• chr15-90970469-G-A
• rs200964554
• NM_003981.4:c.1507C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-90970469-G-A
• chr15-90970469-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003981.4(PRC1):​c.1507C>T​(p.Arg503Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: PRC1 NM_003981.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41461134).

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.1507C>T	p.Arg503Trp	missense	Exon 12 of 15	NP_003972.2	O43663-1
	PRC1	NM_199413.3		c.1507C>T	p.Arg503Trp	missense	Exon 12 of 14	NP_955445.2	O43663-4
	PRC1	NM_001267580.2		c.1384C>T	p.Arg462Trp	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.1507C>T	p.Arg503Trp	missense	Exon 12 of 15	ENSP00000377793.3	O43663-1
	PRC1	ENST00000361188.9	TSL:1	c.1507C>T	p.Arg503Trp	missense	Exon 12 of 14	ENSP00000354679.5	O43663-4
	ENSG00000284946	ENST00000643536.1		n.*1470C>T		non_coding_transcript_exon	Exon 33 of 35	ENSP00000494429.1	A0A2R8YDQ0

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152146 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000278 AC: 7 AN: 251424 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1461624 Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111798

Other (OTH) AF: 0.0000662 AC: 4 AN: 60380

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152264 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74460

African (AFR) AF: 0.0000241 AC: 1 AN: 41542

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.0000151

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.8
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.084	T
Polyphen		0.48	P
Vest4		0.60
MutPred		0.60		Loss of disorder (P = 0.0127)
MVP		0.54
MPC		0.095
ClinPred		0.50	D
GERP RS		3.1
PromoterAI		-0.050	Neutral
Varity_R		0.16
gMVP		0.49
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs200964554; hg19: chr15-91513699; COSMIC: COSV62695195; COSMIC: COSV62695195;