Variant chr4-185408304-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_018359.5(UFSP2):c.963G>A(p.Glu321=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00726 in 1,614,138 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 70 hom. )

Consequence

UFSP2
NM_018359.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.260

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 4-185408304-C-T is Benign according to our data. Variant chr4-185408304-C-T is described in ClinVar as [Benign]. Clinvar id is 779237.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.26 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00494 (752/152300) while in subpopulation NFE AF= 0.00885 (602/68012). AF 95% confidence interval is 0.00827. There are 2 homozygotes in gnomad4. There are 323 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 752 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UFSP2	NM_018359.5 linkuse as main transcript	c.963G>A	p.Glu321=	synonymous_variant	8/12	ENST00000264689.11
UFSP2	NR_028085.2 linkuse as main transcript	n.1034G>A		non_coding_transcript_exon_variant	8/12
UFSP2	NR_144317.2 linkuse as main transcript	n.1059G>A		non_coding_transcript_exon_variant	8/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFSP2	ENST00000264689.11 linkuse as main transcript	c.963G>A	p.Glu321=	synonymous_variant	8/12	2	NM_018359.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00495

AC:

753

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00885

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00557

AC:

1399

AN:

251252

Hom.:

AF XY:

0.00540

AC XY:

733

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00263

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000980

Gnomad FIN exome

AF:

0.00448

Gnomad NFE exome

AF:

0.00978

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00750

AC:

10962

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

5236

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.00226

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00158

Gnomad4 FIN exome

AF:

0.00472

Gnomad4 NFE exome

AF:

0.00901

Gnomad4 OTH exome

AF:

0.00571

GnomAD4 genome

AF:

0.00494

AC:

752

AN:

152300

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

323

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.00885

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00724

Hom.:

Bravo

AF:

0.00462

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00769

EpiControl

AF:

0.00859

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

5.9

DANN

Benign

0.52

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.

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