rs762613748

Variant names:

• chr21-28944455-T-A
• rs762613748
• NM_015565.3:c.3910A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-28944455-T-A
• chr21-28944455-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015565.3(LTN1):​c.3910A>T​(p.Ile1304Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1304V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LTN1 NM_015565.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.613

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10069135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTN1	NM_015565.3	c.3910A>T	p.Ile1304Phe	missense_variant	Exon 22 of 30	ENST00000361371.10	NP_056380.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTN1	ENST00000361371.10	c.3910A>T	p.Ile1304Phe	missense_variant	Exon 22 of 30	1	NM_015565.3	ENSP00000354977.4
LTN1	ENST00000614971.4	c.4048A>T	p.Ile1350Phe	missense_variant	Exon 22 of 30	1		ENSP00000478783.1
LTN1	ENST00000389194.7	c.3910A>T	p.Ile1304Phe	missense_variant	Exon 22 of 30	1		ENSP00000373846.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251254 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135788

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461722 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000278 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.22	T;.;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.86	D;.;D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N;N;.
REVEL	Benign	0.043
Sift	Benign	0.050	D;D;.
Sift4G	Benign	0.14	T;T;T
Polyphen		0.010	B;.;.
Vest4		0.45
MutPred		0.32		Gain of loop (P = 0.069);.;.;
MVP		0.19
MPC		0.74
ClinPred		0.23	T
GERP RS		1.4
Varity_R		0.072
gMVP		0.30

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: rs762613748; hg19: chr21-30316777;