rs1486193742

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-63737994-C-A
• chr20-63737994-C-G
• chr20-63737994-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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

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=0.13726118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIME1	NM_017806.4	c.202C>A	p.Leu68Ile	missense_variant	Exon 4 of 6	ENST00000309546.8	NP_060276.2
LIME1	NM_001305654.2	c.181-14C>A		intron_variant	Intron 3 of 5		NP_001292583.1
LIME1	NM_001305655.2	c.181-14C>A		intron_variant	Intron 3 of 5		NP_001292584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIME1	ENST00000309546.8	c.202C>A	p.Leu68Ile	missense_variant	Exon 4 of 6	1	NM_017806.4	ENSP00000309521.3
ENSG00000273154	ENST00000632538.1	c.520-14C>A		intron_variant	Intron 4 of 5	3		ENSP00000488802.1

Frequencies

GnomAD3 genomes Cov.: 34

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

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: 0.0000234

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Benign	0.13
Sift	Benign	0.033	D;D;.
Sift4G	Uncertain	0.037	D;D;D
Polyphen		0.89	.;P;.
Vest4		0.17
MutPred		0.16		Loss of catalytic residue at L68 (P = 0.0605);Loss of catalytic residue at L68 (P = 0.0605);.;
MVP		0.35
MPC		1.1
ClinPred		0.55	D
GERP RS		2.3
Varity_R		0.11
gMVP		0.060

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

Publications

LitVar

Other links and lift over

dbSNP: rs1486193742; hg19: chr20-62369347;