chr1-230843669-C-A

Variant names:

• chr1-230843669-C-A
• rs150339183
• NM_032800.3:c.612G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032800.3(C1orf198):​c.612G>T​(p.Glu204Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,614,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: C1orf198 NM_032800.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.649
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.056105614).

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.612G>T	p.Glu204Asp	missense	Exon 3 of 4	NP_116189.1	Q9H425-1
	C1orf198	NM_001136494.2		c.498G>T	p.Glu166Asp	missense	Exon 5 of 6	NP_001129966.1	Q9H425-3
	C1orf198	NM_001136495.2		c.222G>T	p.Glu74Asp	missense	Exon 3 of 4	NP_001129967.1	Q9H425-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf198	ENST00000366663.10	TSL:1 MANE Select	c.612G>T	p.Glu204Asp	missense	Exon 3 of 4	ENSP00000355623.5	Q9H425-1
	C1orf198	ENST00000427697.2	TSL:2	c.-40G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	ENSP00000411384.2	E5RFY9
	C1orf198	ENST00000470540.5	TSL:2	c.498G>T	p.Glu166Asp	missense	Exon 5 of 6	ENSP00000428172.1	Q9H425-3

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000677 AC: 17 AN: 251044 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.0000578

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: 0.000163

GnomAD4 exome AF: 0.0000328 AC: 48 AN: 1461812 Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21 AN XY: 727212

African (AFR) AF: 0.00125 AC: 42 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111934

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152352 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74500

African (AFR) AF: 0.00120 AC: 50 AN: 41598

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.000302

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.65
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.089
Sift	Benign	0.035	D
Sift4G	Uncertain	0.057	T
Polyphen		0.97	D
Vest4		0.076
MutPred		0.070		Loss of methylation at R199 (P = 0.1541)
MVP		0.53
MPC		0.25
ClinPred		0.079	T
GERP RS		2.7
Varity_R		0.070
gMVP		0.051
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs150339183; hg19: chr1-230979415;