1-62209976-C-T

Variant names:

• chr1-62209976-C-T
• NM_019079.5:c.1202C>T

Variant summary

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

The NM_019079.5(L1TD1):​c.1202C>T​(p.Ser401Leu) 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: 31)
• Consequence: L1TD1 NM_019079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.128

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 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=0.18688905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L1TD1	NM_019079.5	c.1202C>T	p.Ser401Leu	missense_variant	Exon 4 of 4	ENST00000498273.2	NP_061952.3
L1TD1	NM_001164835.2	c.1202C>T	p.Ser401Leu	missense_variant	Exon 5 of 5		NP_001158307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L1TD1	ENST00000498273.2	c.1202C>T	p.Ser401Leu	missense_variant	Exon 4 of 4	1	NM_019079.5	ENSP00000419901.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1202C>T (p.S401L) alteration is located in exon 5 (coding exon 2) of the L1TD1 gene. This alteration results from a C to T substitution at nucleotide position 1202, causing the serine (S) at amino acid position 401 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.039
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.14
MutPred		0.21		Loss of phosphorylation at S401 (P = 9e-04);
MVP		0.33
MPC		0.038
ClinPred		0.42	T
GERP RS		2.5
Varity_R		0.060
gMVP		0.025

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-62675648; COSMIC: COSV105285952; COSMIC: COSV105285952;