Menu
GeneBe

rs2230199

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2_SupportingPP2BP4_Moderate

The NM_000064.4(C3):c.304C>T(p.Arg102Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. 14/20 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. R102G) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

C3
NM_000064.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00200

Links

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.
PP2
?
Missense variant where missense usually causes diseases, C3
BP4
?
Computational evidence support a benign effect (MetaRNN=0.16331357).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
C3NM_000064.4 linkuse as main transcriptc.304C>T p.Arg102Cys missense_variant 3/41 ENST00000245907.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
C3ENST00000245907.11 linkuse as main transcriptc.304C>T p.Arg102Cys missense_variant 3/411 NM_000064.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461888
Hom.:
0
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
Cadd
Benign
13
Dann
Benign
0.96
DEOGEN2
Benign
0.14
T;T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.34
N;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.6
N;.
REVEL
Benign
0.088
Sift
Benign
0.061
T;.
Sift4G
Uncertain
0.054
T;.
Polyphen
0.67
P;.
Vest4
0.092
MutPred
0.49
Loss of disorder (P = 0.0142);.;
MVP
0.36
MPC
1.1
ClinPred
0.60
D
GERP RS
-0.59
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.42
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs2230199; hg19: chr19-6718387; COSMIC: COSV99836473; COSMIC: COSV99836473;