Genetic Variant LIME1:p.Ala139Val (chr20-63738330-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017806.4(LIME1):c.416C>T(p.Ala139Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,559,242 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

LIME1
NM_017806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0420

Publications

3 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:

ENSG00000273047 (HGNC:):

ENSG00000273047 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008592039).

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.416C>T	p.Ala139Val	missense	Exon 5 of 6	NP_060276.2	Q9H400-1
LIME1	NM_001305654.2		c.381C>T	p.Arg127Arg	synonymous	Exon 5 of 6	NP_001292583.1	A0A087WT39
LIME1	NM_001305655.2		c.381C>T	p.Arg127Arg	synonymous	Exon 5 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.416C>T	p.Ala139Val	missense	Exon 5 of 6	ENSP00000309521.3	Q9H400-1
ENSG00000273047	ENST00000467211.1	TSL:3	c.59C>T	p.Ala20Val	missense	Exon 1 of 2	ENSP00000477118.1	V9GYV3
ENSG00000273154	ENST00000632538.1	TSL:3	c.720C>T	p.Arg240Arg	synonymous	Exon 6 of 6	ENSP00000488802.1	A0A0J9YYD9

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000353

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000203

AC:

AN:

157664

AF XY:

0.000243

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000380

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000827

Gnomad FIN exome

AF:

0.0000937

Gnomad NFE exome

AF:

0.000422

Gnomad OTH exome

AF:

0.000452

GnomAD4 exome

AF:

0.000273

AC:

384

AN:

1406898

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

178

AN XY:

695938

show subpopulations

African (AFR)

AF:

0.0000930

AC:

AN:

32248

American (AMR)

AF:

0.0000264

AC:

AN:

37838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25288

East Asian (EAS)

AF:

0.0000271

AC:

AN:

36872

South Asian (SAS)

AF:

0.00

AC:

AN:

80634

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

42752

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.000329

AC:

358

AN:

1087072

Other (OTH)

AF:

0.000256

AC:

AN:

58490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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

AF:

0.000210

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41588

American (AMR)

AF:

0.000261

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000424

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000382

AC:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

0.094

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.26

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.013

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.40

M_CAP

Benign

0.0095

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.99

PhyloP100

-0.042

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.11

REVEL

Benign

0.012

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.051

MVP

0.10

MPC

0.38

ClinPred

0.024

GERP RS

-4.0

PromoterAI

0.0026

Neutral

(source)

Varity_R

0.019

gMVP

0.040

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over