Genetic Variant LIME1:p.Pro162Leu (chr20-63738399-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017806.4(LIME1):c.485C>T(p.Pro162Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000058 in 1,550,850 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: 33)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

LIME1
NM_017806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.308

Publications

1 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:

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ACMG classification

Classification was made for transcript

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=0.1935229).

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.485C>T	p.Pro162Leu	missense	Exon 5 of 6	NP_060276.2	Q9H400-1
LIME1	NM_001305654.2		c.450C>T	p.Pro150Pro	synonymous	Exon 5 of 6	NP_001292583.1	A0A087WT39
LIME1	NM_001305655.2		c.450C>T	p.Pro150Pro	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.485C>T	p.Pro162Leu	missense	Exon 5 of 6	ENSP00000309521.3	Q9H400-1
ENSG00000273047	ENST00000467211.1	TSL:3	c.128C>T	p.Pro43Leu	missense	Exon 1 of 2	ENSP00000477118.1	V9GYV3
ENSG00000273154	ENST00000632538.1	TSL:3	c.789C>T	p.Pro263Pro	synonymous	Exon 6 of 6	ENSP00000488802.1	A0A0J9YYD9

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000125

AC:

AN:

159662

AF XY:

0.0000228

show subpopulations

Gnomad AFR exome

AF:

0.000230

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:

0.00

GnomAD4 exome

AF:

0.00000500

AC:

AN:

1398650

Hom.:

Cov.:

AF XY:

0.00000869

AC XY:

AN XY:

690406

show subpopulations

African (AFR)

AF:

0.000189

AC:

AN:

31768

American (AMR)

AF:

0.00

AC:

AN:

35574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23932

East Asian (EAS)

AF:

0.00

AC:

AN:

37122

South Asian (SAS)

AF:

0.00

AC:

AN:

78552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

9.25e-7

AC:

AN:

1080750

Other (OTH)

AF:

0.00

AC:

AN:

57748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000483

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000335

Hom.:

Bravo

AF:

0.0000227

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

0.20

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.088

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.68

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.78

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

PhyloP100

0.31

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-8.5

REVEL

Benign

0.037

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0060

Polyphen

0.89

Vest4

0.093

MutPred

0.39

Loss of disorder (P = 0.0381)

MVP

0.52

MPC

0.49

ClinPred

0.26

GERP RS

1.6

PromoterAI

-0.0052

Neutral

(source)

Varity_R

0.45

gMVP

0.096

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over