NM_015565.3:c.4946T>G

Variant names:

• chr21-28932594-A-C
• rs2084219837
• NM_015565.3:c.4946T>G

Variant summary

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

The NM_015565.3(LTN1):​c.4946T>G​(p.Ile1649Arg) variant causes a missense change involving the alteration of a 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: 33)
• Consequence: LTN1 NM_015565.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.87
• Publications: 0 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.4946T>G	p.Ile1649Arg	missense	Exon 28 of 30	NP_056380.3	O94822-1
	LTN1	NM_001320766.2		c.4904T>G	p.Ile1635Arg	missense	Exon 27 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.4946T>G	p.Ile1649Arg	missense	Exon 28 of 30	ENSP00000354977.4	O94822-1
	LTN1	ENST00000614971.4	TSL:1	c.5084T>G	p.Ile1695Arg	missense	Exon 28 of 30	ENSP00000478783.1	O94822-3
	LTN1	ENST00000389194.7	TSL:1	c.4946T>G	p.Ile1649Arg	missense	Exon 28 of 30	ENSP00000373846.3	O94822-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		8.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.65		Loss of helix (P = 0.0795)
MVP		0.26
MPC		0.95
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.73
gMVP		0.67
Mutation Taster		=58/42	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: rs2084219837; hg19: chr21-30304916;