Genetic Variant NM_032800.3:c.746G>T (chr1-230843535-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032800.3(C1orf198):c.746G>T(p.Arg249Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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. R249H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

C1orf198
NM_032800.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.570

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08582413).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1orf198	NM_032800.3	MANE Select	c.746G>T	p.Arg249Leu	missense	Exon 3 of 4	NP_116189.1	Q9H425-1
C1orf198	NM_001136494.2		c.632G>T	p.Arg211Leu	missense	Exon 5 of 6	NP_001129966.1	Q9H425-3
C1orf198	NM_001136495.2		c.356G>T	p.Arg119Leu	missense	Exon 3 of 4	NP_001129967.1	Q9H425-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1orf198	ENST00000366663.10	TSL:1 MANE Select	c.746G>T	p.Arg249Leu	missense	Exon 3 of 4	ENSP00000355623.5	Q9H425-1
C1orf198	ENST00000470540.5	TSL:2	c.632G>T	p.Arg211Leu	missense	Exon 5 of 6	ENSP00000428172.1	Q9H425-3
C1orf198	ENST00000523410.1	TSL:2	c.356G>T	p.Arg119Leu	missense	Exon 3 of 4	ENSP00000430967.1	Q9H425-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

249744

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459932

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726030

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25980

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110748

Other (OTH)

AF:

0.00

AC:

AN:

60276

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.57

M_CAP

Benign

0.017

MetaRNN

Benign

0.086

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.57

PROVEAN

Benign

-1.9

REVEL

Benign

0.020

Sift

Benign

0.082

Sift4G

Benign

0.21

Polyphen

0.052

Vest4

0.14

MutPred

0.17

Loss of MoRF binding (P = 0.0287)

MVP

0.21

MPC

0.58

ClinPred

0.62

GERP RS

2.5

Varity_R

0.050

gMVP

0.12

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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