1-230868197-C-T

Variant names:

• chr1-230868197-C-T
• rs749354516
• NM_032800.3:c.316G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032800.3(C1orf198):​c.316G>A​(p.Val106Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000731 in 1,367,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. V106L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: C1orf198 NM_032800.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.39
• 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]

ENSG00000223393 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

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.316G>A	p.Val106Met	missense	Exon 1 of 4	NP_116189.1	Q9H425-1
	C1orf198	NM_001136494.2		c.202G>A	p.Val68Met	missense	Exon 3 of 6	NP_001129966.1	Q9H425-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf198	ENST00000366663.10	TSL:1 MANE Select	c.316G>A	p.Val106Met	missense	Exon 1 of 4	ENSP00000355623.5	Q9H425-1
	C1orf198	ENST00000470540.5	TSL:2	c.202G>A	p.Val68Met	missense	Exon 3 of 6	ENSP00000428172.1	Q9H425-3
	C1orf198	ENST00000522201.1	TSL:3	c.187G>A	p.Val63Met	missense	Exon 2 of 4	ENSP00000429503.1	E5RI90

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.31e-7 AC: 1 AN: 1367724 Hom.: 0 Cov.: 35 AF XY: 0.00000148 AC XY: 1 AN XY: 675400

African (AFR) AF: 0.00 AC: 0 AN: 27810

American (AMR) AF: 0.00 AC: 0 AN: 33542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24058

East Asian (EAS) AF: 0.00 AC: 0 AN: 31960

South Asian (SAS) AF: 0.00 AC: 0 AN: 77354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5124

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069128

Other (OTH) AF: 0.00 AC: 0 AN: 56810

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.40	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.4
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.52		Gain of disorder (P = 0.0705)
MVP		0.66
MPC		1.8
ClinPred		0.98	D
GERP RS		3.5
PromoterAI		-0.076	Neutral
Varity_R		0.34
gMVP		0.59
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs749354516; hg19: chr1-231003943;