13-38358073-T-A

Position:

• chr13-38358073-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016617.4(UFM1):​c.118-20T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,236,280 control chromosomes in the GnomAD database, including 544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (395 hom., cov: 30)
  • Exomes 𝑓: 0.0031 (149 hom.)
• Consequence: UFM1 NM_016617.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.749

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-38358073-T-A is Benign according to our data. Variant chr13-38358073-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1170579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UFM1	NM_016617.4	c.118-20T>A		intron_variant		ENST00000239878.9	NP_057701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UFM1	ENST00000239878.9	c.118-20T>A		intron_variant		1	NM_016617.4	ENSP00000239878.4
UFM1	ENST00000379649.5	c.172-20T>A		intron_variant		4		ENSP00000368970.1
UFM1	ENST00000437952.1	c.118-20T>A		intron_variant		3		ENSP00000402378.1

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 5943 AN: 140752 Hom.: 390 Cov.: 30

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000231

Gnomad SAS AF: 0.000994

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0133

Gnomad NFE AF: 0.000531

Gnomad OTH AF: 0.0281

GnomAD3 exomes AF: 0.00667 AC: 750 AN: 112394 Hom.: 42 AF XY: 0.00507 AC XY: 322 AN XY: 63552

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.00626

Gnomad ASJ exome AF: 0.000322

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000807

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000476

Gnomad OTH exome AF: 0.00654

GnomAD4 exome AF: 0.00311 AC: 3409 AN: 1095422 Hom.: 149 Cov.: 15 AF XY: 0.00270 AC XY: 1487 AN XY: 550114

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.00761

Gnomad4 ASJ exome AF: 0.000294

Gnomad4 EAS exome AF: 0.0000323

Gnomad4 SAS exome AF: 0.000695

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000318

Gnomad4 OTH exome AF: 0.00901

GnomAD4 genome AF: 0.0424 AC: 5969 AN: 140858 Hom.: 395 Cov.: 30 AF XY: 0.0420 AC XY: 2864 AN XY: 68266

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000232

Gnomad4 SAS AF: 0.000995

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000531

Gnomad4 OTH AF: 0.0278

Alfa AF: 0.0231 Hom.: 31

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2025

- -

Leukodystrophy, hypomyelinating, 14 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 27, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.076
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs545735907; hg19: chr13-38932210;