chr13-38353751-T-G

Variant names:

• chr13-38353751-T-G
• rs2150468
• NM_016617.4:c.60-488T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016617.4(UFM1):​c.60-488T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 151,926 control chromosomes in the GnomAD database, including 56,912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (56912 hom., cov: 30)
• Consequence: UFM1 NM_016617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P
• hypomyelinating leukodystrophy 6

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016617.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFM1	NM_016617.4	MANE Select	c.60-488T>G		intron	N/A	NP_057701.1	P61960-1
	UFM1	NM_001286704.2		c.114-488T>G		intron	N/A	NP_001273633.1	P61960-2
	UFM1	NM_001286703.2		c.60-494T>G		intron	N/A	NP_001273632.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFM1	ENST00000239878.9	TSL:1 MANE Select	c.60-488T>G		intron	N/A	ENSP00000239878.4	P61960-1
	UFM1	ENST00000891124.1		c.138-488T>G		intron	N/A	ENSP00000561183.1
	UFM1	ENST00000379649.5	TSL:4	c.114-488T>G		intron	N/A	ENSP00000368970.1	P61960-2

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127575 AN: 151808 Hom.: 56901 Cov.: 30

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.874

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.840 AC: 127626 AN: 151926 Hom.: 56912 Cov.: 30 AF XY: 0.845 AC XY: 62772 AN XY: 74298

African (AFR) AF: 0.506 AC: 20945 AN: 41370

American (AMR) AF: 0.928 AC: 14171 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3244 AN: 3470

East Asian (EAS) AF: 0.988 AC: 5087 AN: 5148

South Asian (SAS) AF: 0.959 AC: 4620 AN: 4816

European-Finnish (FIN) AF: 0.983 AC: 10419 AN: 10594

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66123 AN: 67938

Other (OTH) AF: 0.875 AC: 1846 AN: 2110

Alfa AF: 0.886 Hom.: 5437

Bravo AF: 0.823

Asia WGS AF: 0.942 AC: 3273 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.75
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2150468; hg19: chr13-38927888;