Variant 4-185400469-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_018359.5(UFSP2):c.1333G>A(p.Gly445Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

UFSP2
NM_018359.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.53

Variant links:

Genes affected

UFSP2 (HGNC:25640): (UFM1 specific peptidase 2) This gene encodes a highly conserved cysteine protease. The protein cleaves two C-terminal residues from ubiquitin-fold modifier 1, a ubiquitin-like post-translational modifier protein. Activation of ubiquitin-fold modifier 1 by the encoded protein exposes a C-terminal glycine residue that allows interaction with other proteins and transfer to its target protein. An allelic variant of this gene has been associated with Beukes hip dysplasia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

UFSP2 links:

ANKRD37 (HGNC:29593): (ankyrin repeat domain 37) Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD37 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.933

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UFSP2	NM_018359.5 linkuse as main transcript	c.1333G>A	p.Gly445Arg	missense_variant	12/12	ENST00000264689.11
ANKRD37	XM_017008176.2 linkuse as main transcript	c.*692C>T		3_prime_UTR_variant	4/4
UFSP2	NR_028085.2 linkuse as main transcript	n.1404G>A		non_coding_transcript_exon_variant	12/12
UFSP2	NR_144317.2 linkuse as main transcript	n.1532G>A		non_coding_transcript_exon_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFSP2	ENST00000264689.11 linkuse as main transcript	c.1333G>A	p.Gly445Arg	missense_variant	12/12	2	NM_018359.5	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250800

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461006

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

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:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hip dysplasia, Beukes type

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Benign

0.11

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.093

MetaRNN

Pathogenic

0.93

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.8

REVEL

Uncertain

0.37

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.75

MutPred

0.84

Gain of solvent accessibility (P = 0.0584);

MVP

0.60

MPC

0.35

ClinPred

0.99

GERP RS

4.3

Varity_R

0.83

gMVP

0.96

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over