NM_003981.4:c.1550G>A

Variant names:

• chr15-90970426-C-T
• rs201630358
• NM_003981.4:c.1550G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_003981.4(PRC1):​c.1550G>A​(p.Arg517Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,610,704 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 0.000046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: PRC1 NM_003981.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.47
• Publications: 5 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.42374495).

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.1550G>A	p.Arg517Gln	missense	Exon 12 of 15	NP_003972.2	O43663-1
	PRC1	NM_199413.3		c.1550G>A	p.Arg517Gln	missense	Exon 12 of 14	NP_955445.2	O43663-4
	PRC1	NM_001267580.2		c.1427G>A	p.Arg476Gln	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.1550G>A	p.Arg517Gln	missense	Exon 12 of 15	ENSP00000377793.3	O43663-1
	PRC1	ENST00000361188.9	TSL:1	c.1550G>A	p.Arg517Gln	missense	Exon 12 of 14	ENSP00000354679.5	O43663-4
	ENSG00000284946	ENST00000643536.1		n.*1513G>A		non_coding_transcript_exon	Exon 33 of 35	ENSP00000494429.1	A0A2R8YDQ0

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152114 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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251304 AF XY: 0.0000442

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000108 AC: 158 AN: 1458590 Hom.: 0 Cov.: 30 AF XY: 0.000113 AC XY: 82 AN XY: 725788

African (AFR) AF: 0.0000898 AC: 3 AN: 33406

American (AMR) AF: 0.0000224 AC: 1 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26106

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000128 AC: 142 AN: 1109070

Other (OTH) AF: 0.0000830 AC: 5 AN: 60272

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152114 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74296

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

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	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.36
Sift	Benign	0.088	T
Sift4G	Benign	0.088	T
Polyphen		1.0	D
Vest4		0.39
MVP		0.70
MPC		0.24
ClinPred		0.35	T
GERP RS		6.2
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.48
Mutation Taster		=80/20	polymorphism

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: rs201630358; hg19: chr15-91513656; COSMIC: COSV62694821; COSMIC: COSV62694821;