20-63737994-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017806.4(LIME1):​c.202C>T​(p.Leu68Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000828 in 1,570,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

LIME1
NM_017806.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.172
Variant links:
Genes affected
LIME1 (HGNC:26016): (Lck interacting transmembrane adaptor 1) This gene encodes a transmembrane adaptor protein that links the T and B-cell receptor stimulation to downstream signaling pathways via its association with the Src family kinases Lck and Lyn, respectively. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Mar 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.20300987).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LIME1NM_017806.4 linkc.202C>T p.Leu68Phe missense_variant Exon 4 of 6 ENST00000309546.8 NP_060276.2 Q9H400-1
LIME1NM_001305654.2 linkc.181-14C>T intron_variant Intron 3 of 5 NP_001292583.1 Q9H400A0A087WT39
LIME1NM_001305655.2 linkc.181-14C>T intron_variant Intron 3 of 5 NP_001292584.1 Q9H400A0A087WT39

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LIME1ENST00000309546.8 linkc.202C>T p.Leu68Phe missense_variant Exon 4 of 6 1 NM_017806.4 ENSP00000309521.3 Q9H400-1
ENSG00000273154ENST00000632538.1 linkc.520-14C>T intron_variant Intron 4 of 5 3 ENSP00000488802.1 A0A0J9YYD9

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152146
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000569
AC:
1
AN:
175894
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
96628
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000137
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000776
AC:
11
AN:
1418424
Hom.:
0
Cov.:
50
AF XY:
0.00000996
AC XY:
7
AN XY:
702686
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000101
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152146
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.202C>T (p.L68F) alteration is located in exon 4 (coding exon 3) of the LIME1 gene. This alteration results from a C to T substitution at nucleotide position 202, causing the leucine (L) at amino acid position 68 to be replaced by a phenylalanine (F). 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
0.25
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.079
.;T;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.37
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.59
T;T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.20
T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
1.3
.;L;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.0
D;D;.
REVEL
Benign
0.16
Sift
Uncertain
0.014
D;D;.
Sift4G
Uncertain
0.017
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.16
MVP
0.52
MPC
1.2
ClinPred
0.80
D
GERP RS
2.3
Varity_R
0.17
gMVP
0.094

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1486193742; hg19: chr20-62369347; API