Variant rs1033946108 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_016617.4(UFM1):c.241C>T(p.Arg81Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,607,616 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

UFM1
NM_016617.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.93

Variant links:

Genes affected

UFM1 (HGNC:20597): (ubiquitin fold modifier 1) UFM1 is a ubiquitin-like protein that is conjugated to target proteins by E1-like activating enzyme UBA5 (UBE1DC1; MIM 610552) and E2-like conjugating enzyme UFC1 (MIM 610554) in a manner analogous to ubiquitylation (see UBE2M; MIM 603173) (Komatsu et al., 2004 [PubMed 15071506]).[supplied by OMIM, Dec 2008]

UFM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 13-38360761-C-T is Pathogenic according to our data. Variant chr13-38360761-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 559446.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-38360761-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UFM1	NM_016617.4 linkuse as main transcript	c.241C>T	p.Arg81Cys	missense_variant	6/6	ENST00000239878.9	NP_057701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UFM1	ENST00000239878.9 linkuse as main transcript	c.241C>T	p.Arg81Cys	missense_variant	6/6	1	NM_016617.4	ENSP00000239878	P1	P61960-1
UFM1	ENST00000379649.5 linkuse as main transcript	c.295C>T	p.Arg99Cys	missense_variant	6/6	4		ENSP00000368970		P61960-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249062

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134704

show subpopulations

Gnomad AFR exome

AF:

0.0000618

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1455624

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724136

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151992

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

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

Bravo

AF:

0.0000453

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Leukodystrophy, hypomyelinating, 14

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.19

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.40

.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Uncertain

-0.14

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-7.2

D;D

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;.

Polyphen

1.0

.;D

Vest4

0.71

MutPred

0.64

.;Gain of catalytic residue at R79 (P = 0.0028);

MVP

0.31

MPC

1.1

ClinPred

1.0

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.90

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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