Genetic Variant LIME1:p.Ala26Thr (chr20-63737625-G-A) – 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_017806.4(LIME1):c.76G>A(p.Ala26Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,936 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LIME1
NM_017806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.792

Publications

0 publications found

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]

LIME1 links:

ENSG00000273154 (HGNC:):

ENSG00000273154 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=0.025279015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017806.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIME1	NM_017806.4	MANE Select	c.76G>A	p.Ala26Thr	missense	Exon 2 of 6	NP_060276.2	Q9H400-1
LIME1	NM_001305654.2		c.76G>A	p.Ala26Thr	missense	Exon 2 of 6	NP_001292583.1	A0A087WT39
LIME1	NM_001305655.2		c.76G>A	p.Ala26Thr	missense	Exon 2 of 6	NP_001292584.1	A0A087WT39

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIME1	ENST00000309546.8	TSL:1 MANE Select	c.76G>A	p.Ala26Thr	missense	Exon 2 of 6	ENSP00000309521.3	Q9H400-1
ENSG00000273154	ENST00000632538.1	TSL:3	c.415G>A	p.Ala139Thr	missense	Exon 3 of 6	ENSP00000488802.1	A0A0J9YYD9
LIME1	ENST00000899472.1		c.76G>A	p.Ala26Thr	missense	Exon 2 of 5	ENSP00000569531.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000463

AC:

AN:

216182

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:

0.00

Gnomad OTH exome

AF:

0.000188

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1446936

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32896

American (AMR)

AF:

0.00

AC:

AN:

43224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25790

East Asian (EAS)

AF:

0.00

AC:

AN:

38672

South Asian (SAS)

AF:

0.00

AC:

AN:

83938

European-Finnish (FIN)

AF:

0.0000198

AC:

AN:

50564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106464

Other (OTH)

AF:

0.0000167

AC:

AN:

59716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000833

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.032

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.61

M_CAP

Benign

0.0056

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.0

PhyloP100

-0.79

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.4

REVEL

Benign

0.042

Sift

Benign

0.24

Sift4G

Benign

0.35

Polyphen

0.0020

Vest4

0.24

MutPred

0.25

Loss of catalytic residue at A26 (P = 0.1226)

MVP

0.18

MPC

0.43

ClinPred

0.028

GERP RS

-0.43

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

gMVP

0.16

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over