1-62207110-C-T

Variant names:

• chr1-62207110-C-T
• rs1421031051
• NM_019079.5:c.482C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019079.5(L1TD1):​c.482C>T​(p.Pro161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P161H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: L1TD1 NM_019079.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• Publications: 0 publications found

Genes affected

L1TD1 (HGNC:25595): (LINE1 type transposase domain containing 1) Predicted to enable single-stranded RNA binding activity. Predicted to be involved in transposition, RNA-mediated. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054178417).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019079.5. 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
	L1TD1	NM_019079.5	MANE Select	c.482C>T	p.Pro161Leu	missense	Exon 3 of 4	NP_061952.3
	L1TD1	NM_001164835.2		c.482C>T	p.Pro161Leu	missense	Exon 4 of 5	NP_001158307.1	Q5T7N2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L1TD1	ENST00000498273.2	TSL:1 MANE Select	c.482C>T	p.Pro161Leu	missense	Exon 3 of 4	ENSP00000419901.1	Q5T7N2
	L1TD1	ENST00000928897.1		c.482C>T	p.Pro161Leu	missense	Exon 4 of 5	ENSP00000598956.1
	L1TD1	ENST00000928898.1		c.482C>T	p.Pro161Leu	missense	Exon 3 of 4	ENSP00000598957.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452624 Hom.: 0 Cov.: 78 AF XY: 0.00000139 AC XY: 1 AN XY: 721664

African (AFR) AF: 0.0000600 AC: 2 AN: 33360

American (AMR) AF: 0.00 AC: 0 AN: 42764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39552

South Asian (SAS) AF: 0.00 AC: 0 AN: 85332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106882

Other (OTH) AF: 0.00 AC: 0 AN: 60078

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.8
DANN	Benign	0.81
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.44
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.027
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.012	D
Polyphen		0.21	B
Vest4		0.061
MutPred		0.22		Loss of methylation at K159 (P = 0.113)
MVP		0.29
MPC		0.042
ClinPred		0.10	T
GERP RS		0.34
Varity_R		0.039
gMVP		0.033
Mutation Taster		=100/0	polymorphism

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: rs1421031051; hg19: chr1-62672782; COSMIC: COSV63133645; COSMIC: COSV63133645;