13-38362173-A-G

Variant names:

• chr13-38362173-A-G
• rs2485783
• NM_016617.4:c.*1395A>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.*1395A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,198 control chromosomes in the GnomAD database, including 59,712 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 0.87 (59704 hom., cov: 31)
  • Exomes 𝑓: 1.0 (8 hom.)
• Consequence: UFM1 NM_016617.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFM1	NM_016617.4	MANE Select	c.*1395A>G		3_prime_UTR	Exon 6 of 6	NP_057701.1
	UFM1	NR_104584.2		n.1783A>G		non_coding_transcript_exon	Exon 7 of 7
	UFM1	NR_104585.2		n.1682A>G		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFM1	ENST00000239878.9	TSL:1 MANE Select	c.*1395A>G		3_prime_UTR	Exon 6 of 6	ENSP00000239878.4

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132459 AN: 152064 Hom.: 59687 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.892

GnomAD4 exome AF: 1.00 AC: 16 AN: 16 Hom.: 8 Cov.: 0 AF XY: 1.00 AC XY: 12 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 14 AN: 14

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.871 AC: 132515 AN: 152182 Hom.: 59704 Cov.: 31 AF XY: 0.875 AC XY: 65109 AN XY: 74410

African (AFR) AF: 0.614 AC: 25467 AN: 41464

American (AMR) AF: 0.938 AC: 14354 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3243 AN: 3472

East Asian (EAS) AF: 0.988 AC: 5099 AN: 5160

South Asian (SAS) AF: 0.959 AC: 4627 AN: 4824

European-Finnish (FIN) AF: 0.984 AC: 10435 AN: 10610

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.974 AC: 66226 AN: 68028

Other (OTH) AF: 0.893 AC: 1890 AN: 2116

Alfa AF: 0.907 Hom.: 18315

Bravo AF: 0.857

Asia WGS AF: 0.948 AC: 3297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.0
DANN	Benign	0.86
PhyloP100		0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2485783; hg19: chr13-38936310;