1-161157678-C-G

Variant names:

• chr1-161157678-C-G
• NM_016406.4:c.317C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1 PM2 PM5 PP3_Moderate

The NM_016406.4(UFC1):​c.317C>G​(p.Thr106Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,678 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. T106I) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UFC1 NM_016406.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.77

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]

ENSG00000224985 (HGNC:):

ACMG classification

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 2 benign (78%) in NM_016406.4
• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-161157678-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 559447.Status of the report is criteria_provided_single_submitter, 1 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.876

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UFC1	NM_016406.4	c.317C>G	p.Thr106Arg	missense_variant	Exon 4 of 6	ENST00000368003.6	NP_057490.2
UFC1	XM_005245254.2	c.317C>G	p.Thr106Arg	missense_variant	Exon 4 of 5		XP_005245311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UFC1	ENST00000368003.6	c.317C>G	p.Thr106Arg	missense_variant	Exon 4 of 6	1	NM_016406.4	ENSP00000356982.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461678 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727144

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.73		Loss of ubiquitination at K105 (P = 0.0382);
MVP		0.72
MPC		1.1
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.95
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-161127468;