Genetic Variant UFSP1:p.Glu95Gly (chr7-100889216-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001430944.2(UFSP1):c.284A>G(p.Glu95Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. E95K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UFSP1
NM_001430944.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.98

Publications

0 publications found

Variant links:

Genes affected

UFSP1 (HGNC:33821): (UFM1 specific peptidase 1 (inactive)) This gene encodes a protein that is similar to other Ufm1-specific proteases. Studies in mouse determined that Ufsp1 releases Ufm1 (ubiquitin-fold modifier 1) from its bound conjugated complexes which also makes it into an active form. Because the human UFSP1 protein is shorter on the N-terminus and lacks a conserved Cys active site, it is predicted to be non-functional.[provided by RefSeq, Nov 2009]

UFSP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.936

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001430944.2. 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
	UFSP1	NM_001430944.2	MANE Select	c.284A>G	p.Glu95Gly	missense	Exon 1 of 1	NP_001417873.1	Q6NVU6
	UFSP1	NM_001015072.4		c.56A>G	p.Glu19Gly	missense	Exon 1 of 1	NP_001015072.2	A0AAR1ZLH9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFSP1	ENST00000672365.3	MANE Select	c.284A>G	p.Glu95Gly	missense	Exon 1 of 1	ENSP00000499910.2	Q6NVU6
	UFSP1	ENST00000388761.4	TSL:6	c.56A>G	p.Glu19Gly	missense	Exon 1 of 1	ENSP00000373413.2	A0AAR1ZLH9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1440924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715292

African (AFR)

AF:

0.00

AC:

AN:

33148

American (AMR)

AF:

0.00

AC:

AN:

43230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24982

East Asian (EAS)

AF:

0.00

AC:

AN:

39498

South Asian (SAS)

AF:

0.00

AC:

AN:

84220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5082

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102940

Other (OTH)

AF:

0.00

AC:

AN:

59344

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

-0.014

PhyloP100

2.0

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-6.7

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.51

MutPred

0.90

Loss of helix (P = 0.1299)

MVP

0.57

MPC

0.42

ClinPred

1.0

GERP RS

4.4

PromoterAI

-0.00090

Neutral

(source)

Varity_R

0.97

gMVP

0.78

Mutation Taster

=44/56

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over