rs1221036716

Variant names:

• chr20-63737559-C-T
• rs1221036716
• NM_017806.4:c.10C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017806.4(LIME1):​c.10C>T​(p.Pro4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,433,946 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LIME1 NM_017806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.518
• 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: 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=0.06197056).

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.10C>T	p.Pro4Ser	missense	Exon 2 of 6	NP_060276.2	Q9H400-1
	LIME1	NM_001305654.2		c.10C>T	p.Pro4Ser	missense	Exon 2 of 6	NP_001292583.1	A0A087WT39
	LIME1	NM_001305655.2		c.10C>T	p.Pro4Ser	missense	Exon 2 of 6	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.10C>T	p.Pro4Ser	missense	Exon 2 of 6	ENSP00000309521.3	Q9H400-1
	ENSG00000273154	ENST00000632538.1	TSL:3	c.349C>T	p.Pro117Ser	missense	Exon 3 of 6	ENSP00000488802.1	A0A0J9YYD9
	LIME1	ENST00000899472.1		c.10C>T	p.Pro4Ser	missense	Exon 2 of 5	ENSP00000569531.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000482 AC: 1 AN: 207288 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: 0.0000109

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1433946 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 712176

African (AFR) AF: 0.00 AC: 0 AN: 31828

American (AMR) AF: 0.0000244 AC: 1 AN: 41066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25218

East Asian (EAS) AF: 0.00 AC: 0 AN: 37388

South Asian (SAS) AF: 0.00 AC: 0 AN: 82464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100922

Other (OTH) AF: 0.00 AC: 0 AN: 59150

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.2
DANN	Benign	0.85
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.52
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.029
Sift	Benign	0.17	T
Sift4G	Benign	0.35	T
Polyphen		0.0070	B
Vest4		0.041
MutPred		0.24		Gain of sheet (P = 0.0266)
MVP		0.20
MPC		0.39
ClinPred		0.024	T
GERP RS		1.9
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.026
gMVP		0.14
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1221036716; hg19: chr20-62368912;