13-38350126-T-C

Position:

• chr13-38350126-T-C

Variant summary

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

The ENST00000239878.9(UFM1):​c.59+71T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 1,614,116 control chromosomes in the GnomAD database, including 739,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (59507 hom., cov: 32)
  • Exomes 𝑓: 0.96 (680421 hom.)
• Consequence: UFM1 ENST00000239878.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.585

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-38350126-T-C is Benign according to our data. Variant chr13-38350126-T-C is described in ClinVar as [Benign]. Clinvar id is 1168539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UFM1	NM_016617.4	c.59+71T>C		intron_variant		ENST00000239878.9	NP_057701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UFM1	ENST00000239878.9	c.59+71T>C		intron_variant		1	NM_016617.4	ENSP00000239878	P1
LINC00571	ENST00000454060.2	n.134A>G		non_coding_transcript_exon_variant	1/8	3

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132162 AN: 152112 Hom.: 59491 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.891

GnomAD3 exomes AF: 0.947 AC: 237348 AN: 250692 Hom.: 113393 AF XY: 0.953 AC XY: 129361 AN XY: 135792

Gnomad AFR exome AF: 0.601

Gnomad AMR exome AF: 0.966

Gnomad ASJ exome AF: 0.934

Gnomad EAS exome AF: 0.987

Gnomad SAS exome AF: 0.960

Gnomad FIN exome AF: 0.984

Gnomad NFE exome AF: 0.972

Gnomad OTH exome AF: 0.957

GnomAD4 exome AF: 0.963 AC: 1407866 AN: 1461886 Hom.: 680421 Cov.: 82 AF XY: 0.964 AC XY: 700958 AN XY: 727242

Gnomad4 AFR exome AF: 0.601

Gnomad4 AMR exome AF: 0.964

Gnomad4 ASJ exome AF: 0.933

Gnomad4 EAS exome AF: 0.989

Gnomad4 SAS exome AF: 0.961

Gnomad4 FIN exome AF: 0.984

Gnomad4 NFE exome AF: 0.974

Gnomad4 OTH exome AF: 0.945

GnomAD4 genome AF: 0.869 AC: 132217 AN: 152230 Hom.: 59507 Cov.: 32 AF XY: 0.873 AC XY: 64980 AN XY: 74450

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.937

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.959

Gnomad4 FIN AF: 0.984

Gnomad4 NFE AF: 0.973

Gnomad4 OTH AF: 0.893

Alfa AF: 0.954 Hom.: 110270

Bravo AF: 0.855

Asia WGS AF: 0.947 AC: 3295 AN: 3478

EpiCase AF: 0.971

EpiControl AF: 0.968

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs2231332; hg19: chr13-38924263;