Genetic Variant C1orf198:p.Gly99Arg (chr1-230868218-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

Publications

0 publications found

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:

ENSG00000223393 (HGNC:):

ENSG00000223393 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15914336).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032800.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf198	NM_032800.3	MANE Select	c.295G>A	p.Gly99Arg	missense	Exon 1 of 4	NP_116189.1	Q9H425-1
	C1orf198	NM_001136494.2		c.181G>A	p.Gly61Arg	missense	Exon 3 of 6	NP_001129966.1	Q9H425-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1orf198	ENST00000366663.10	TSL:1 MANE Select	c.295G>A	p.Gly99Arg	missense	Exon 1 of 4	ENSP00000355623.5	Q9H425-1
C1orf198	ENST00000470540.5	TSL:2	c.181G>A	p.Gly61Arg	missense	Exon 3 of 6	ENSP00000428172.1	Q9H425-3
C1orf198	ENST00000522201.1	TSL:3	c.166G>A	p.Gly56Arg	missense	Exon 2 of 4	ENSP00000429503.1	E5RI90

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

152006

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000597

AC:

AN:

134084

AF XY:

0.0000535

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000194

Gnomad OTH exome

AF:

0.000269

GnomAD4 exome

AF:

0.0000180

AC:

AN:

1385402

Hom.:

Cov.:

AF XY:

0.0000204

AC XY:

AN XY:

684794

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28638

American (AMR)

AF:

0.000340

AC:

AN:

35282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24374

East Asian (EAS)

AF:

0.00

AC:

AN:

33348

South Asian (SAS)

AF:

0.00

AC:

AN:

78836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5400

European-Non Finnish (NFE)

AF:

0.00000836

AC:

AN:

1076540

Other (OTH)

AF:

0.0000696

AC:

AN:

57488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41530

American (AMR)

AF:

0.000261

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67946

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000350

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0097

Eigen

Benign

0.18

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

1.5

PROVEAN

Benign

0.36

REVEL

Benign

0.082

Sift

Benign

0.35

Sift4G

Benign

0.16

Polyphen

0.99

Vest4

0.43

MutPred

0.24

Loss of methylation at R98 (P = 0.0353)

MVP

0.43

MPC

2.1

ClinPred

0.13

GERP RS

3.5

PromoterAI

0.18

Neutral

(source)

Varity_R

0.084

gMVP

0.60

Mutation Taster

=81/19

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over