13-38358075-T-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016617.4(UFM1):​c.118-18T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000264 in 1,134,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000026 ( 0 hom. )

Consequence

UFM1
NM_016617.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.69

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • leukodystrophy, hypomyelinating, 14
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • hypomyelinating leukodystrophy 6
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 13-38358075-T-A is Benign according to our data. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-38358075-T-A is described in CliVar as Likely_benign. Clinvar id is 1946887.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UFM1NM_016617.4 linkc.118-18T>A intron_variant Intron 3 of 5 ENST00000239878.9 NP_057701.1 P61960-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UFM1ENST00000239878.9 linkc.118-18T>A intron_variant Intron 3 of 5 1 NM_016617.4 ENSP00000239878.4 P61960-1
UFM1ENST00000379649.5 linkc.172-18T>A intron_variant Intron 3 of 5 4 ENSP00000368970.1 P61960-2
UFM1ENST00000437952.1 linkc.118-18T>A intron_variant Intron 2 of 3 3 ENSP00000402378.1 H0Y614

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000264
AC:
3
AN:
1134712
Hom.:
0
Cov.:
15
AF XY:
0.00000176
AC XY:
1
AN XY:
568218
show subpopulations
African (AFR)
AF:
0.000135
AC:
3
AN:
22302
American (AMR)
AF:
0.00
AC:
0
AN:
24796
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20640
East Asian (EAS)
AF:
0.00
AC:
0
AN:
31508
South Asian (SAS)
AF:
0.00
AC:
0
AN:
57358
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
44766
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3352
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
883390
Other (OTH)
AF:
0.00
AC:
0
AN:
46600
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.392
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
May 03, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
6.0
DANN
Benign
0.63
PhyloP100
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1879197048; hg19: chr13-38932212; API