Genetic Variant NM_015565.3:c.426C>A (chr21-28984842-G-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015565.3(LTN1):c.426C>A(p.Pro142Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,502 control chromosomes in the GnomAD database, including 11,659 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1879 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9780 hom. )

Consequence

LTN1
NM_015565.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.210

Variant links:

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]

LTN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP7

Synonymous conserved (PhyloP=0.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTN1	NM_015565.3 link	c.426C>A	p.Pro142Pro	synonymous_variant	Exon 4 of 30	ENST00000361371.10	NP_056380.3
LTN1	NM_001320766.2 link	c.426C>A	p.Pro142Pro	synonymous_variant	Exon 4 of 29		NP_001307695.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LTN1	ENST00000361371.10 link	c.426C>A	p.Pro142Pro	synonymous_variant	Exon 4 of 30	1	NM_015565.3	ENSP00000354977.4	O94822-1
LTN1	ENST00000389194.7 link	c.426C>A	p.Pro142Pro	synonymous_variant	Exon 4 of 30	1		ENSP00000373846.3	O94822-1
LTN1	ENST00000389195.7 link	c.426C>A	p.Pro142Pro	synonymous_variant	Exon 4 of 13	1		ENSP00000373847.3	H7BYG8

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

21981

AN:

152000

Hom.:

1883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0607

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.124

AC:

31133

AN:

251264

Hom.:

2206

AF XY:

0.118

AC XY:

16022

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.160

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.0626

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.111

AC:

162170

AN:

1461384

Hom.:

9780

Cov.:

AF XY:

0.109

AC XY:

79602

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.0658

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.145

AC:

21991

AN:

152118

Hom.:

1879

Cov.:

AF XY:

0.141

AC XY:

10501

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0607

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.118

Hom.:

1539

Bravo

AF:

0.155

Asia WGS

AF:

0.137

AC:

480

AN:

3478

EpiCase

AF:

0.110

EpiControl

AF:

0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.2

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over