dbSNP rs774489801: C1orf198:p.Gly99Trp (chr1-230868218-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032800.3(C1orf198):c.295G>T(p.Gly99Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G99R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

C1orf198
NM_032800.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37470752).

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>T	p.Gly99Trp	missense	Exon 1 of 4	NP_116189.1	Q9H425-1
	C1orf198	NM_001136494.2		c.181G>T	p.Gly61Trp	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>T	p.Gly99Trp	missense	Exon 1 of 4	ENSP00000355623.5	Q9H425-1
C1orf198	ENST00000470540.5	TSL:2	c.181G>T	p.Gly61Trp	missense	Exon 3 of 6	ENSP00000428172.1	Q9H425-3
C1orf198	ENST00000522201.1	TSL:3	c.166G>T	p.Gly56Trp	missense	Exon 2 of 4	ENSP00000429503.1	E5RI90

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.22e-7

AC:

AN:

1385400

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

684792

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

28638

American (AMR)

AF:

0.00

AC:

AN:

35282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24374

East Asian (EAS)

AF:

0.00

AC:

AN:

33346

South Asian (SAS)

AF:

0.00

AC:

AN:

78836

European-Finnish (FIN)

AF:

0.0000220

AC:

AN:

45496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5400

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076540

Other (OTH)

AF:

0.00

AC:

AN:

57488

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

1.5

PROVEAN

Benign

0.0

REVEL

Benign

0.13

Sift

Benign

0.18

Sift4G

Uncertain

0.052

Polyphen

1.0

Vest4

0.47

MutPred

0.32

Loss of disorder (P = 0.009)

MVP

0.30

MPC

2.2

ClinPred

0.74

GERP RS

3.5

PromoterAI

-0.092

Neutral

(source)

Varity_R

0.082

gMVP

0.57

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over