chr1-230868218-C-T

Variant summary

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

The NM_032800.3(C1orf198):​c.295G>A​(p.Gly99Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,537,516 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 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

C1orf198
NM_032800.3 missense

Scores

2
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54
Variant links:
Genes affected
C1orf198 (HGNC:25900): (chromosome 1 open reading frame 198) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.15914336).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
C1orf198NM_032800.3 linkuse as main transcriptc.295G>A p.Gly99Arg missense_variant 1/4 ENST00000366663.10 NP_116189.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
C1orf198ENST00000366663.10 linkuse as main transcriptc.295G>A p.Gly99Arg missense_variant 1/41 NM_032800.3 ENSP00000355623 P1Q9H425-1
ENST00000439341.2 linkuse as main transcript upstream_gene_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
152006
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.0000294
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000597
AC:
8
AN:
134084
Hom.:
0
AF XY:
0.0000535
AC XY:
4
AN XY:
74736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000255
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000194
Gnomad OTH exome
AF:
0.000269
GnomAD4 exome
AF:
0.0000180
AC:
25
AN:
1385402
Hom.:
0
Cov.:
34
AF XY:
0.0000204
AC XY:
14
AN XY:
684794
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000340
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:
0.00000836
Gnomad4 OTH exome
AF:
0.0000696
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152114
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.0000453
ExAC
AF:
0.0000350
AC:
3

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 GeneticsOct 05, 2021The c.295G>A (p.G99R) alteration is located in exon 1 (coding exon 1) of the C1orf198 gene. This alteration results from a G to A substitution at nucleotide position 295, causing the glycine (G) at amino acid position 99 to be replaced by an arginine (R). 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
Pathogenic
0.77
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0097
T;.;T
Eigen
Benign
0.18
Eigen_PC
Benign
0.15
FATHMM_MKL
Benign
0.12
N
LIST_S2
Uncertain
0.90
D;D;T
M_CAP
Pathogenic
0.51
D
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;.;.
MutationTaster
Benign
1.0
D;N;N
PROVEAN
Benign
0.36
N;N;N
REVEL
Benign
0.082
Sift
Benign
0.35
T;D;D
Sift4G
Benign
0.16
T;D;.
Polyphen
0.99
D;.;.
Vest4
0.43
MutPred
0.24
Loss of methylation at R98 (P = 0.0353);.;.;
MVP
0.43
MPC
2.1
ClinPred
0.13
T
GERP RS
3.5
Varity_R
0.084
gMVP
0.60

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

LitVar

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

Other links and lift over

dbSNP: rs774489801; hg19: chr1-231003964; API