NM_003981.4:c.1612C>T

Variant names:

• chr15-90969584-G-A
• rs761737564
• NM_003981.4:c.1612C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003981.4(PRC1):​c.1612C>T​(p.Arg538Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,612,682 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 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: PRC1 NM_003981.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.347
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11570671).

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.1612C>T	p.Arg538Cys	missense	Exon 13 of 15	NP_003972.2	O43663-1
	PRC1	NM_199413.3		c.1612C>T	p.Arg538Cys	missense	Exon 13 of 14	NP_955445.2	O43663-4
	PRC1	NM_001267580.2		c.1489C>T	p.Arg497Cys	missense	Exon 12 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.1612C>T	p.Arg538Cys	missense	Exon 13 of 15	ENSP00000377793.3	O43663-1
	PRC1	ENST00000361188.9	TSL:1	c.1612C>T	p.Arg538Cys	missense	Exon 13 of 14	ENSP00000354679.5	O43663-4
	ENSG00000284946	ENST00000643536.1		n.*1575C>T		non_coding_transcript_exon	Exon 34 of 35	ENSP00000494429.1	A0A2R8YDQ0

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152064 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000680 AC: 17 AN: 250036 AF XY: 0.0000814

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000648

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1460618 Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21 AN XY: 726582

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.0000225 AC: 1 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.000468 AC: 25 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111288

Other (OTH) AF: 0.0000663 AC: 4 AN: 60330

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152064 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74264

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15256

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000412 AC: 5

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	0.093
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.35
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.98	D
Vest4		0.27
MutPred		0.58		Loss of MoRF binding (P = 6e-04)
MVP		0.61
MPC		0.41
ClinPred		0.32	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.40
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs761737564; hg19: chr15-91512814;