Variant 1-230868197-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032800.3(C1orf198):c.316G>C(p.Val106Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000476 in 1,519,806 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 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

C1orf198
NM_032800.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.39

Variant links:

Genes affected

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

C1orf198 links:

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=0.2605757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf198	NM_032800.3 linkuse as main transcript	c.316G>C	p.Val106Leu	missense_variant	1/4	ENST00000366663.10	NP_116189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf198	ENST00000366663.10 linkuse as main transcript	c.316G>C	p.Val106Leu	missense_variant	1/4	1	NM_032800.3	ENSP00000355623	P1	Q9H425-1
C1orf198	ENST00000470540.5 linkuse as main transcript	c.202G>C	p.Val68Leu	missense_variant	3/6	2		ENSP00000428172		Q9H425-3
C1orf198	ENST00000522201.1 linkuse as main transcript	c.187G>C	p.Val63Leu	missense_variant	2/4	3		ENSP00000429503
C1orf198	ENST00000427697.2 linkuse as main transcript	c.-229+615G>C		intron_variant		2		ENSP00000411384

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000618

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000226

AC:

AN:

114826

Hom.:

AF XY:

0.000217

AC XY:

AN XY:

64424

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000138

Gnomad ASJ exome

AF:

0.000141

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000522

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000490

AC:

670

AN:

1367720

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

299

AN XY:

675398

show subpopulations

Gnomad4 AFR exome

AF:

0.000108

Gnomad4 AMR exome

AF:

0.000119

Gnomad4 ASJ exome

AF:

0.0000416

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000607

Gnomad4 OTH exome

AF:

0.000211

GnomAD4 genome

AF:

0.000348

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000425

Hom.:

Bravo

AF:

0.000344

ExAC

AF:

0.000162

AC:

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 submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.316G>C (p.V106L) alteration is located in exon 1 (coding exon 1) of the C1orf198 gene. This alteration results from a G to C substitution at nucleotide position 316, causing the valine (V) at amino acid position 106 to be replaced by a leucine (L). 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

0.93

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.047

T;.;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.87

D;D;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

1.0

D;D;D

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.28

Sift

Benign

0.056

T;T;D

Sift4G

Benign

0.18

T;T;.

Polyphen

1.0

D;.;.

Vest4

0.53

MutPred

0.48

Loss of ubiquitination at K104 (P = 0.1453);.;.;

MVP

0.63

MPC

0.91

ClinPred

0.18

GERP RS

3.5

Varity_R

0.31

gMVP

0.54

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over