chr1-161154065-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM5PP3_Moderate

The ENST00000368003.6(UFC1):ā€‹c.68G>Cā€‹(p.Arg23Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,116 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R23Q) has been classified as Pathogenic.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

UFC1
ENST00000368003.6 missense

Scores

9
8
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.81
Variant links:
Genes affected
UFC1 (HGNC:26941): (ubiquitin-fold modifier conjugating enzyme 1) UFC1 is an E2-like conjugating enzyme for ubiquitin-fold modifier-1 (UFM1; MIM 610553) (Komatsu et al., 2004 [PubMed 15071506]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM1
In a chain Ubiquitin-fold modifier-conjugating enzyme 1 (size 166) in uniprot entity UFC1_HUMAN there are 7 pathogenic changes around while only 1 benign (88%) in ENST00000368003.6
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr1-161154065-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 559448.Status of the report is no_assertion_criteria_provided, 0 stars.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UFC1NM_016406.4 linkuse as main transcriptc.68G>C p.Arg23Pro missense_variant 1/6 ENST00000368003.6 NP_057490.2
UFC1XM_005245254.2 linkuse as main transcriptc.68G>C p.Arg23Pro missense_variant 1/5 XP_005245311.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UFC1ENST00000368003.6 linkuse as main transcriptc.68G>C p.Arg23Pro missense_variant 1/61 NM_016406.4 ENSP00000356982 P1
ENST00000420498.1 linkuse as main transcriptn.74C>G non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152116
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.45
T
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
1.0
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.034
D
MetaRNN
Pathogenic
0.89
D
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Pathogenic
3.0
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-5.4
D
REVEL
Uncertain
0.58
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0090
D
Polyphen
1.0
D
Vest4
0.85
MutPred
0.68
Loss of MoRF binding (P = 0.0099);
MVP
0.89
MPC
1.2
ClinPred
1.0
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.99
gMVP
0.93

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1181612302; hg19: chr1-161123855; API