chr1-34197289-C-T

Position:

• chr1-34197289-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001134734.2(C1orf94):​c.385C>T​(p.Leu129Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000214 in 1,400,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: C1orf94 NM_001134734.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1orf94	NM_001134734.2	c.385C>T	p.Leu129Phe	missense_variant	2/7	ENST00000488417.2
C1orf94	NM_032884.5	c.-186C>T		5_prime_UTR_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1orf94	ENST00000488417.2	c.385C>T	p.Leu129Phe	missense_variant	2/7	1	NM_001134734.2	P1
C1orf94	ENST00000373374.7	c.-186C>T		5_prime_UTR_variant	2/7	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1400836 Hom.: 0 Cov.: 30 AF XY: 0.00000434 AC XY: 3 AN XY: 691172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000377

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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.385C>T (p.L129F) alteration is located in exon 2 (coding exon 2) of the C1orf94 gene. This alteration results from a C to T substitution at nucleotide position 385, causing the leucine (L) at amino acid position 129 to be replaced by a phenylalanine (F). 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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.056	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	0.69	D;D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.13		Gain of sheet (P = 0.0827);
MVP		0.75
MPC		0.26
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.41
gMVP		0.18

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: chr1-34662890;