Genetic Variant NM_003981.4:c.1438A>C (chr15-90974159-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003981.4(PRC1):c.1438A>C(p.Asn480His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N480D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PRC1
NM_003981.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.102

Publications

0 publications found

Variant links:

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 links:

ENSG00000284946 (HGNC:):

ENSG00000284946 links:

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

PRC1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.073857784).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRC1	NM_003981.4	MANE Select	c.1438A>C	p.Asn480His	missense	Exon 11 of 15	NP_003972.2	O43663-1
PRC1	NM_199413.3		c.1438A>C	p.Asn480His	missense	Exon 11 of 14	NP_955445.2	O43663-4
PRC1	NM_001267580.2		c.1315A>C	p.Asn439His	missense	Exon 10 of 13	NP_001254509.2	O43663-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRC1	ENST00000394249.8	TSL:1 MANE Select	c.1438A>C	p.Asn480His	missense	Exon 11 of 15	ENSP00000377793.3	O43663-1
PRC1	ENST00000361188.9	TSL:1	c.1438A>C	p.Asn480His	missense	Exon 11 of 14	ENSP00000354679.5	O43663-4
ENSG00000284946	ENST00000643536.1		n.*1401A>C		non_coding_transcript_exon	Exon 32 of 35	ENSP00000494429.1	A0A2R8YDQ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.6

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.055

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.76

M_CAP

Benign

0.0049

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.10

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.5

REVEL

Benign

0.048

Sift

Benign

0.15

Sift4G

Benign

0.13

Polyphen

0.0010

Vest4

0.21

MutPred

0.40

Gain of ubiquitination at K484 (P = 0.1103)

MVP

0.28

MPC

0.078

ClinPred

0.034

GERP RS

1.9

Varity_R

0.042

gMVP

0.24

Mutation Taster

=87/13

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over