rs200676589

Variant names:

• chr1-230843535-C-A
• rs200676589
• NM_032800.3:c.746G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-230843535-C-A
• chr1-230843535-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570

Genes affected

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

ACMG classification

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=0.08582413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf198	NM_032800.3	c.746G>T	p.Arg249Leu	missense_variant	Exon 3 of 4	ENST00000366663.10	NP_116189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf198	ENST00000366663.10	c.746G>T	p.Arg249Leu	missense_variant	Exon 3 of 4	1	NM_032800.3	ENSP00000355623.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459932 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T;.;T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.57	T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.086	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PROVEAN	Benign	-1.9	N;N;D;D
REVEL	Benign	0.020
Sift	Benign	0.082	T;T;T;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.052	B;.;.;.
Vest4		0.14
MutPred		0.17		Loss of MoRF binding (P = 0.0287);.;.;.;
MVP		0.21
MPC		0.58
ClinPred		0.62	D
GERP RS		2.5
Varity_R		0.050
gMVP		0.12

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

LitVar

Other links and lift over

dbSNP: rs200676589; hg19: chr1-230979281;