13-41458321-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014059.3(RGCC):​c.86C>G​(p.Ser29Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000757 in 1,584,670 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

RGCC
NM_014059.3 missense

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.20625442).
BS2
High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RGCCNM_014059.3 linkc.86C>G p.Ser29Trp missense_variant Exon 2 of 5 ENST00000379359.4 NP_054778.2 Q9H4X1-1
RGCCXM_047430282.1 linkc.86C>G p.Ser29Trp missense_variant Exon 2 of 3 XP_047286238.1
RGCCXR_007063677.1 linkn.244C>G non_coding_transcript_exon_variant Exon 2 of 4
RGCCXR_941565.2 linkn.244C>G non_coding_transcript_exon_variant Exon 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RGCCENST00000379359.4 linkc.86C>G p.Ser29Trp missense_variant Exon 2 of 5 1 NM_014059.3 ENSP00000368664.3 Q9H4X1-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000247
AC:
5
AN:
202210
Hom.:
0
AF XY:
0.0000178
AC XY:
2
AN XY:
112054
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000636
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000128
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000109
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000768
AC:
11
AN:
1432454
Hom.:
0
Cov.:
31
AF XY:
0.00000562
AC XY:
4
AN XY:
711598
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000471
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000772
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000362
Gnomad4 OTH exome
AF:
0.0000335
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000168
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.86C>G (p.S29W) alteration is located in exon 2 (coding exon 2) of the RGCC gene. This alteration results from a C to G substitution at nucleotide position 86, causing the serine (S) at amino acid position 29 to be replaced by a tryptophan (W). 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Benign
0.54
D
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-3.8
D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.020
D
Polyphen
0.91
P
Vest4
0.26
MutPred
0.30
Loss of disorder (P = 0.0037);
MVP
0.21
MPC
1.4
ClinPred
0.78
D
GERP RS
4.5
Varity_R
0.50
gMVP
0.44

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

LitVar

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

Other links and lift over

dbSNP: rs772565358; hg19: chr13-42032457; API