Variant 15-90974159-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003981.4(PRC1):c.1438A>G(p.Asn480Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PRC1
NM_003981.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.102

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06933984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRC1	NM_003981.4 link	c.1438A>G	p.Asn480Asp	missense_variant	Exon 11 of 15	ENST00000394249.8	NP_003972.2	O43663-1A0A024RC67

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRC1	ENST00000394249.8 link	c.1438A>G	p.Asn480Asp	missense_variant	Exon 11 of 15	1	NM_003981.4	ENSP00000377793.3	O43663-1
ENSG00000284946	ENST00000643536.1 link	n.*1401A>G		non_coding_transcript_exon_variant	Exon 32 of 35			ENSP00000494429.1	A0A2R8YDQ0
ENSG00000284946	ENST00000643536.1 link	n.*1401A>G		3_prime_UTR_variant	Exon 32 of 35			ENSP00000494429.1	A0A2R8YDQ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1438A>G (p.N480D) alteration is located in exon 11 (coding exon 11) of the PRC1 gene. This alteration results from a A to G substitution at nucleotide position 1438, causing the asparagine (N) at amino acid position 480 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.5

DANN

Benign

0.93

DEOGEN2

Benign

0.089

T;.;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0076

MetaRNN

Benign

0.069

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

L;L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.064

Sift

Benign

0.58

T;T;T

Sift4G

Benign

0.62

T;T;T

Polyphen

0.042

B;.;B

Vest4

0.18

MutPred

0.44

Loss of catalytic residue at N480 (P = 0.0373);Loss of catalytic residue at N480 (P = 0.0373);.;

MVP

0.31

MPC

0.099

ClinPred

0.076

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over