20-63737994-C-A

Variant names:

• chr20-63737994-C-A
• rs1486193742
• NM_017806.4:c.202C>A

Variant summary

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

The NM_017806.4(LIME1):​c.202C>A​(p.Leu68Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L68F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: LIME1 NM_017806.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 0 publications found

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]

ENSG00000273154 (HGNC:):

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=0.13726118).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIME1	NM_017806.4	MANE Select	c.202C>A	p.Leu68Ile	missense	Exon 4 of 6	NP_060276.2	Q9H400-1
	LIME1	NM_001305654.2		c.181-14C>A		intron	N/A	NP_001292583.1	A0A087WT39
	LIME1	NM_001305655.2		c.181-14C>A		intron	N/A	NP_001292584.1	A0A087WT39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIME1	ENST00000309546.8	TSL:1 MANE Select	c.202C>A	p.Leu68Ile	missense	Exon 4 of 6	ENSP00000309521.3	Q9H400-1
	ENSG00000273154	ENST00000632538.1	TSL:3	c.520-14C>A		intron	N/A	ENSP00000488802.1	A0A0J9YYD9
	LIME1	ENST00000899472.1		c.272C>A	p.Pro91His	missense	Exon 3 of 5	ENSP00000569531.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 175894 AF XY: 0.00

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: 0.00

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418424 Hom.: 0 Cov.: 50 AF XY: 0.00000142 AC XY: 1 AN XY: 702686

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

African (AFR) AF: 0.00 AC: 0 AN: 32302

American (AMR) AF: 0.00 AC: 0 AN: 40650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25484

East Asian (EAS) AF: 0.00 AC: 0 AN: 37680

South Asian (SAS) AF: 0.00 AC: 0 AN: 81762

European-Finnish (FIN) AF: 0.0000234 AC: 1 AN: 42668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093440

Other (OTH) AF: 0.00 AC: 0 AN: 58786

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.17
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.13
Sift	Benign	0.033	D
Sift4G	Uncertain	0.037	D
Polyphen		0.89	P
Vest4		0.17
MutPred		0.16		Loss of catalytic residue at L68 (P = 0.0605)
MVP		0.35
MPC		1.1
ClinPred		0.55	D
GERP RS		2.3
PromoterAI		0.015	Neutral
Varity_R		0.11
gMVP		0.060
Mutation Taster		=99/1	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: rs1486193742; hg19: chr20-62369347;