rs1879197048

Variant names:

• chr13-38358075-T-A
• rs1879197048
• NM_016617.4:c.118-18T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.69
• Publications: 0 publications found

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

ACMG classification

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
UFM1	NM_016617.4	c.118-18T>A		intron_variant	Intron 3 of 5	ENST00000239878.9	NP_057701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UFM1	ENST00000239878.9	c.118-18T>A		intron_variant	Intron 3 of 5	1	NM_016617.4	ENSP00000239878.4
UFM1	ENST00000379649.5	c.172-18T>A		intron_variant	Intron 3 of 5	4		ENSP00000368970.1
UFM1	ENST00000437952.1	c.118-18T>A		intron_variant	Intron 2 of 3	3		ENSP00000402378.1

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

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

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

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

Other links and lift over

dbSNP: rs1879197048; hg19: chr13-38932212;