21-28931172-AT-A

Variant names:

• chr21-28931172-AT-A
• rs1389074071
• NM_015565.3:c.5220delA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015565.3(LTN1):​c.5220delA​(p.Lys1740AsnfsTer37) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LTN1 NM_015565.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.657
• Publications: 1 publications found

Genes affected

LTN1 (HGNC:13082): (listerin E3 ubiquitin protein ligase 1) Like most RING finger proteins, LTN1 functions as an E3 ubiquitin ligase (Chu et al., 2009 [PubMed 19196968]).[supplied by OMIM, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015565.3. 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
	LTN1	NM_015565.3	MANE Select	c.5220delA	p.Lys1740AsnfsTer37	frameshift	Exon 29 of 30	NP_056380.3	O94822-1
	LTN1	NM_001320766.2		c.5178delA	p.Lys1726AsnfsTer37	frameshift	Exon 28 of 29	NP_001307695.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTN1	ENST00000361371.10	TSL:1 MANE Select	c.5220delA	p.Lys1740AsnfsTer37	frameshift	Exon 29 of 30	ENSP00000354977.4	O94822-1
	LTN1	ENST00000614971.4	TSL:1	c.5358delA	p.Lys1786AsnfsTer37	frameshift	Exon 29 of 30	ENSP00000478783.1	O94822-3
	LTN1	ENST00000389194.7	TSL:1	c.5220delA	p.Lys1740AsnfsTer37	frameshift	Exon 29 of 30	ENSP00000373846.3	O94822-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Neurodevelopmental disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66
Mutation Taster		=11/189	disease causing

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: rs1389074071; hg19: chr21-30303494;