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GeneBe

13-41466888-T-C

Variant summary

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

The NM_014059.3(RGCC):c.301T>C(p.Ser101Pro) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RGCC
NM_014059.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.478
Variant links:
Genes affected
RGCC (HGNC:20369): (regulator of cell cycle) This gene is thought to regulate cell cycle progression. It is induced by p53 in response to DNA damage, or by sublytic levels of complement system proteins that result in activation of the cell cycle. The encoded protein localizes to the cytoplasm during interphase and to centrosomes during mitosis. The protein forms a complex with polo-like kinase 1. The protein also translocates to the nucleus in response to treatment with complement system proteins, and can associate with and increase the kinase activity of cell division cycle 2 protein. In different assays and cell types, overexpression of this protein has been shown to activate or suppress cell cycle progression. [provided by RefSeq, Jul 2008]

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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=0.07255873).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RGCCNM_014059.3 linkuse as main transcriptc.301T>C p.Ser101Pro missense_variant 3/5 ENST00000379359.4
RGCCXR_941565.2 linkuse as main transcriptn.727T>C non_coding_transcript_exon_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RGCCENST00000379359.4 linkuse as main transcriptc.301T>C p.Ser101Pro missense_variant 3/51 NM_014059.3 P1Q9H4X1-1
RGCCENST00000487837.1 linkuse as main transcriptn.132T>C non_coding_transcript_exon_variant 2/33

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 01, 2022The c.301T>C (p.S101P) alteration is located in exon 3 (coding exon 3) of the RGCC gene. This alteration results from a T to C substitution at nucleotide position 301, causing the serine (S) at amino acid position 101 to be replaced by a proline (P). 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
0.088
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.52
Cadd
Benign
13
Dann
Benign
0.93
DEOGEN2
Benign
0.11
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.073
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.10
Sift
Benign
0.14
T
Sift4G
Benign
0.23
T
Polyphen
0.0010
B
Vest4
0.19
MutPred
0.15
Loss of phosphorylation at S101 (P = 0.0306);
MVP
0.095
MPC
0.83
ClinPred
0.087
T
GERP RS
-6.8
Varity_R
0.30
gMVP
0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-42041024; API