rs749354516

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-230868197-C-G
• chr1-230868197-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032800.3(C1orf198):​c.316G>C​(p.Val106Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000476 in 1,519,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (0 hom.)
• Consequence: C1orf198 NM_032800.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.39
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2605757).

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>C	p.Val106Leu	missense	Exon 1 of 4	NP_116189.1	Q9H425-1
	C1orf198	NM_001136494.2		c.202G>C	p.Val68Leu	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>C	p.Val106Leu	missense	Exon 1 of 4	ENSP00000355623.5	Q9H425-1
	C1orf198	ENST00000470540.5	TSL:2	c.202G>C	p.Val68Leu	missense	Exon 3 of 6	ENSP00000428172.1	Q9H425-3
	C1orf198	ENST00000522201.1	TSL:3	c.187G>C	p.Val63Leu	missense	Exon 2 of 4	ENSP00000429503.1	E5RI90

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000618

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000226 AC: 26 AN: 114826 AF XY: 0.000217

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000138

Gnomad ASJ exome AF: 0.000141

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000522

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000490 AC: 670 AN: 1367720 Hom.: 0 Cov.: 35 AF XY: 0.000443 AC XY: 299 AN XY: 675398

African (AFR) AF: 0.000108 AC: 3 AN: 27810

American (AMR) AF: 0.000119 AC: 4 AN: 33542

Ashkenazi Jewish (ASJ) AF: 0.0000416 AC: 1 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: 0.000195 AC: 1 AN: 5124

European-Non Finnish (NFE) AF: 0.000607 AC: 649 AN: 1069124

Other (OTH) AF: 0.000211 AC: 12 AN: 56810

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152086 Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24 AN XY: 74294

African (AFR) AF: 0.000217 AC: 9 AN: 41440

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000425 Hom.: 0

Bravo AF: 0.000344

ExAC AF: 0.000162 AC: 11

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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.4
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.28
Sift	Benign	0.056	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.48		Loss of ubiquitination at K104 (P = 0.1453)
MVP		0.63
MPC		0.91
ClinPred		0.18	T
GERP RS		3.5
PromoterAI		-0.045	Neutral
Varity_R		0.31
gMVP		0.54
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs749354516; hg19: chr1-231003943;