Genetic Variant L1TD1:p.Pro161Arg (chr1-62207110-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019079.5(L1TD1):c.482C>G(p.Pro161Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.0000021 ( 0 hom. )

Consequence

L1TD1
NM_019079.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.438

Publications

0 publications found

Variant links:

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]

L1TD1 links:

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ACMG classification

Classification was made for transcript

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=0.05655396).

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>G	p.Pro161Arg	missense	Exon 3 of 4	NP_061952.3
	L1TD1	NM_001164835.2		c.482C>G	p.Pro161Arg	missense	Exon 4 of 5	NP_001158307.1	Q5T7N2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
L1TD1	ENST00000498273.2	TSL:1 MANE Select	c.482C>G	p.Pro161Arg	missense	Exon 3 of 4	ENSP00000419901.1	Q5T7N2
L1TD1	ENST00000928897.1		c.482C>G	p.Pro161Arg	missense	Exon 4 of 5	ENSP00000598956.1
L1TD1	ENST00000928898.1		c.482C>G	p.Pro161Arg	missense	Exon 3 of 4	ENSP00000598957.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000440

AC:

AN:

227184

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1452624

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721664

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33360

American (AMR)

AF:

0.00

AC:

AN:

42764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25870

East Asian (EAS)

AF:

0.00

AC:

AN:

39552

South Asian (SAS)

AF:

0.00

AC:

AN:

85332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1106882

Other (OTH)

AF:

0.0000333

AC:

AN:

60078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.5

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.047

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.47

M_CAP

Benign

0.0023

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.44

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.0

REVEL

Benign

0.023

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.032

Polyphen

0.39

Vest4

0.072

MutPred

0.25

Gain of MoRF binding (P = 0.054)

MVP

0.22

MPC

0.043

ClinPred

0.049

GERP RS

0.34

Varity_R

0.060

gMVP

0.023

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over