21-28984842-G-T

Variant names:

• chr21-28984842-G-T
• rs2245431
• NM_015565.3:c.426C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 19 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: Benign. The variant received -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	c.426C>A	p.Pro142Pro	synonymous_variant	Exon 4 of 30	ENST00000361371.10	NP_056380.3
LTN1	NM_001320766.2	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	Appris	UniProt
LTN1	ENST00000361371.10	c.426C>A	p.Pro142Pro	synonymous_variant	Exon 4 of 30	1	NM_015565.3	ENSP00000354977.4
LTN1	ENST00000389194.7	c.426C>A	p.Pro142Pro	synonymous_variant	Exon 4 of 30	1		ENSP00000373846.3
LTN1	ENST00000389195.7	c.426C>A	p.Pro142Pro	synonymous_variant	Exon 4 of 13	1		ENSP00000373847.3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21981 AN: 152000 Hom.: 1883 Cov.: 32

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

GnomAD2 exomes AF: 0.124 AC: 31133 AN: 251264 AF XY: 0.118

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 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.: 33 AF XY: 0.109 AC XY: 79602 AN XY: 726978

African (AFR) AF: 0.247 AC: 8249 AN: 33456

American (AMR) AF: 0.168 AC: 7508 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3373 AN: 26128

East Asian (EAS) AF: 0.103 AC: 4104 AN: 39680

South Asian (SAS) AF: 0.102 AC: 8807 AN: 86236

European-Finnish (FIN) AF: 0.0658 AC: 3514 AN: 53414

Middle Eastern (MID) AF: 0.115 AC: 665 AN: 5768

European-Non Finnish (NFE) AF: 0.106 AC: 118255 AN: 1111620

Other (OTH) AF: 0.127 AC: 7695 AN: 60370

GnomAD4 genome AF: 0.145 AC: 21991 AN: 152118 Hom.: 1879 Cov.: 32 AF XY: 0.141 AC XY: 10501 AN XY: 74362

African (AFR) AF: 0.236 AC: 9792 AN: 41480

American (AMR) AF: 0.154 AC: 2361 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3468

East Asian (EAS) AF: 0.148 AC: 765 AN: 5174

South Asian (SAS) AF: 0.114 AC: 547 AN: 4810

European-Finnish (FIN) AF: 0.0607 AC: 643 AN: 10592

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7061 AN: 67994

Other (OTH) AF: 0.140 AC: 294 AN: 2104

Alfa AF: 0.123 Hom.: 2047

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
PhyloP100		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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: rs2245431; hg19: chr21-30357163; COSMIC: COSV63733173;