Variant 1-28531856-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_001381865.2(RCC1):c.127G>A(p.Gly43Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RCC1
NM_001381865.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.97

Variant links:

Genes affected

RCC1 (HGNC:1913): (regulator of chromosome condensation 1) Enables several functions, including guanyl-nucleotide exchange factor activity; nucleosomal DNA binding activity; and protein heterodimerization activity. Involved in several processes, including G1/S transition of mitotic cell cycle; regulation of mitotic nuclear division; and spindle organization. Located in chromatin; cytoplasm; and nucleus. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RCC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.884

PP5

Variant 1-28531856-G-A is Pathogenic according to our data. Variant chr1-28531856-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2687490.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCC1	NM_001381865.2 linkuse as main transcript	c.127G>A	p.Gly43Ser	missense_variant	6/13	ENST00000683442.1	NP_001368794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCC1	ENST00000683442.1 linkuse as main transcript	c.127G>A	p.Gly43Ser	missense_variant	6/13		NM_001381865.2	ENSP00000508074	P1	P18754-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1440190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715002

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

See cases

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Newman Lab, University of Manchester

Jan 11, 2024

This is a novel disease-gene association -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

D;.;D;T;D;D;D;.;.;D

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.99

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;.;D;D;.;D;.;D;D;D

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.88

D;D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

0.83

MutationAssessor

Pathogenic

3.6

H;.;.;.;H;.;H;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-5.9

D;.;D;D;D;D;D;D;D;D

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0040

D;.;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0070

D;.;D;.;D;D;D;D;D;D

Polyphen

1.0

D;D;.;.;D;.;D;D;.;.

Vest4

0.87

MutPred

0.68

Gain of phosphorylation at G43 (P = 0.0841);.;Gain of phosphorylation at G43 (P = 0.0841);Gain of phosphorylation at G43 (P = 0.0841);Gain of phosphorylation at G43 (P = 0.0841);Gain of phosphorylation at G43 (P = 0.0841);Gain of phosphorylation at G43 (P = 0.0841);.;.;Gain of phosphorylation at G43 (P = 0.0841);

MVP

0.97

MPC

1.3

ClinPred

1.0

GERP RS

5.9

Varity_R

0.91

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over