13-38350046-C-T

Variant names:

• chr13-38350046-C-T
• rs750631146
• NM_016617.4:c.50C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PP3_Moderate BP6

The NM_001286704.2(UFM1):​c.-69C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000372 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UFM1 NM_001286704.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.93
• 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]

LINC00571 (HGNC:43721): (long intergenic non-protein coding RNA 571)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852
• BP6: Variant 13-38350046-C-T is Benign according to our data. Variant chr13-38350046-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3034495.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286704.2. 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.50C>T	p.Pro17Leu	missense	Exon 2 of 6	NP_057701.1	P61960-1
	UFM1	NM_001286704.2		c.-69C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001273633.1	P61960-2
	UFM1	NM_001286703.2		c.50C>T	p.Pro17Leu	missense	Exon 2 of 6	NP_001273632.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFM1	ENST00000239878.9	TSL:1 MANE Select	c.50C>T	p.Pro17Leu	missense	Exon 2 of 6	ENSP00000239878.4	P61960-1
	UFM1	ENST00000379649.5	TSL:4	c.-69C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000368970.1	P61960-2
	UFM1	ENST00000891124.1		c.50C>T	p.Pro17Leu	missense	Exon 2 of 7	ENSP00000561183.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152210 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461894 Hom.: 0 Cov.: 89 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152210 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74370

African (AFR) AF: 0.0000724 AC: 3 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	UFM1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	-0.12	T
PhyloP100		4.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D
Polyphen		0.99	D
Vest4		0.79
MutPred		0.71		Gain of sheet (P = 0.0125)
MVP		0.36
MPC		1.2
ClinPred		1.0	D
GERP RS		5.0
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.75
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs750631146; hg19: chr13-38924183;