rs1670756750

Variant names:

• chr1-62206875-G-A
• rs1670756750
• NM_019079.5:c.247G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019079.5(L1TD1):​c.247G>A​(p.Gly83Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,032 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: L1TD1 NM_019079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.828
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07380068).

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.247G>A	p.Gly83Arg	missense	Exon 3 of 4	NP_061952.3
	L1TD1	NM_001164835.2		c.247G>A	p.Gly83Arg	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.247G>A	p.Gly83Arg	missense	Exon 3 of 4	ENSP00000419901.1	Q5T7N2
	L1TD1	ENST00000928897.1		c.247G>A	p.Gly83Arg	missense	Exon 4 of 5	ENSP00000598956.1
	L1TD1	ENST00000928898.1		c.247G>A	p.Gly83Arg	missense	Exon 3 of 4	ENSP00000598957.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461032 Hom.: 0 Cov.: 79 AF XY: 0.00 AC XY: 0 AN XY: 726816

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111732

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.4
DANN	Benign	0.77
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.83
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.0040
Sift	Benign	0.034	D
Sift4G	Benign	0.48	T
Polyphen		0.18	B
Vest4		0.14
MutPred		0.39		Gain of MoRF binding (P = 0.0264)
MVP		0.25
MPC		0.046
ClinPred		0.094	T
GERP RS		1.1
Varity_R		0.042
gMVP		0.017
Mutation Taster		=98/2	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: rs1670756750; hg19: chr1-62672547;