rs141586492

Variant names:

• chr1-209783054-C-G
• rs141586492
• NM_152485.4:c.581G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-209783054-C-G
• chr1-209783054-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152485.4(C1orf74):​c.581G>C​(p.Cys194Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. C194Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C1orf74 NM_152485.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23
• Publications: 2 publications found

Genes affected

C1orf74 (HGNC:26319): (chromosome 1 open reading frame 74)

ENSG00000289700 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.923

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152485.4. 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
	C1orf74	NM_152485.4	MANE Select	c.581G>C	p.Cys194Ser	missense	Exon 2 of 2	NP_689698.1	Q96LT6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf74	ENST00000294811.2	TSL:1 MANE Select	c.581G>C	p.Cys194Ser	missense	Exon 2 of 2	ENSP00000294811.1	Q96LT6
	ENSG00000289700	ENST00000696133.1		c.*595G>C		3_prime_UTR	Exon 10 of 10	ENSP00000512426.1	A0A8Q3SJ75
	C1orf74	ENST00000885064.1		c.581G>C	p.Cys194Ser	missense	Exon 2 of 2	ENSP00000555123.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.2
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.80		Gain of disorder (P = 5e-04)
MVP		0.55
MPC		0.98
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.95
gMVP		0.79
Mutation Taster		=34/66	disease causing

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: rs141586492; hg19: chr1-209956399;