chr1-62207092-A-G

Position:

• chr1-62207092-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000498273.2(L1TD1):​c.464A>G​(p.Asn155Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: L1TD1 ENST00000498273.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00300

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038418353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L1TD1	NM_019079.5	c.464A>G	p.Asn155Ser	missense_variant	3/4	ENST00000498273.2	NP_061952.3
L1TD1	NM_001164835.2	c.464A>G	p.Asn155Ser	missense_variant	4/5		NP_001158307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L1TD1	ENST00000498273.2	c.464A>G	p.Asn155Ser	missense_variant	3/4	1	NM_019079.5	ENSP00000419901.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000415 AC: 1 AN: 241238 Hom.: 0 AF XY: 0.00000763 AC XY: 1 AN XY: 131042

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000558

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 Cov.: 79

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.464A>G (p.N155S) alteration is located in exon 4 (coding exon 1) of the L1TD1 gene. This alteration results from a A to G substitution at nucleotide position 464, causing the asparagine (N) at amino acid position 155 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.91
DANN	Benign	0.79
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.016
Sift	Benign	0.58	T
Sift4G	Benign	0.56	T
Polyphen		0.0020	B
Vest4		0.055
MutPred		0.090		Gain of phosphorylation at N155 (P = 0.0349);
MVP		0.12
MPC		0.036
ClinPred		0.010	T
GERP RS		0.79
Varity_R		0.024
gMVP		0.0075

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: rs765928286; hg19: chr1-62672764;