chr1-34212294-C-A

Position:

• chr1-34212294-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1orf94	NM_001134734.2	c.1609C>A	p.Gln537Lys	missense_variant	6/7	ENST00000488417.2
C1orf94	NM_032884.5	c.1039C>A	p.Gln347Lys	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1orf94	ENST00000488417.2	c.1609C>A	p.Gln537Lys	missense_variant	6/7	1	NM_001134734.2	P1
C1orf94	ENST00000373374.7	c.1039C>A	p.Gln347Lys	missense_variant	6/7	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.1609C>A (p.Q537K) alteration is located in exon 6 (coding exon 6) of the C1orf94 gene. This alteration results from a C to A substitution at nucleotide position 1609, causing the glutamine (Q) at amino acid position 537 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.7	.;L
MutationTaster	Benign	0.74	D;D
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-34677895;