1-34212294-C-A

Variant names:

• chr1-34212294-C-A
• NM_001134734.2:c.1609C>A

Variant summary

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

The NM_001134734.2(C1orf94):​c.1609C>A​(p.Gln537Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: C1orf94 NM_001134734.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.52
• Publications: 0 publications found

Genes affected

C1orf94 (HGNC:28250): (chromosome 1 open reading frame 94)

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, 0.766

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134734.2. 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
	C1orf94	NM_001134734.2	MANE Select	c.1609C>A	p.Gln537Lys	missense	Exon 6 of 7	NP_001128206.1	Q6P1W5-1
	C1orf94	NM_032884.5		c.1039C>A	p.Gln347Lys	missense	Exon 6 of 7	NP_116273.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf94	ENST00000488417.2	TSL:1 MANE Select	c.1609C>A	p.Gln537Lys	missense	Exon 6 of 7	ENSP00000435634.1	Q6P1W5-1
	C1orf94	ENST00000373374.7	TSL:1	c.1039C>A	p.Gln347Lys	missense	Exon 6 of 7	ENSP00000362472.3	Q6P1W5-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.30
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.5
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.23		Gain of methylation at Q537 (P = 3e-04)
MVP		0.45
MPC		0.18
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.80
gMVP		0.48
Mutation Taster		=85/15	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

hg19: chr1-34677895;