chr20-63738434-A-C

Variant names:

• chr20-63738434-A-C
• NM_017806.4:c.520A>C

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.520A>C​(p.Lys174Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: LIME1 NM_017806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.234
• 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=0.07219702).

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.520A>C	p.Lys174Gln	missense	Exon 5 of 6	NP_060276.2	Q9H400-1
	LIME1	NM_001305654.2		c.485A>C	p.Gln162Pro	missense	Exon 5 of 6	NP_001292583.1	A0A087WT39
	LIME1	NM_001305655.2		c.485A>C	p.Gln162Pro	missense	Exon 5 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.520A>C	p.Lys174Gln	missense	Exon 5 of 6	ENSP00000309521.3	Q9H400-1
	ENSG00000273154	ENST00000632538.1	TSL:3	c.824A>C	p.Gln275Pro	missense	Exon 6 of 6	ENSP00000488802.1	A0A0J9YYD9
	ENSG00000273047	ENST00000467211.1	TSL:3	c.163A>C	p.Lys55Gln	missense	Exon 1 of 2	ENSP00000477118.1	V9GYV3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

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	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.2
DANN	Benign	0.57
DEOGEN2	Benign	0.055	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.23
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.037
Sift	Benign	0.16	T
Sift4G	Benign	0.26	T
Polyphen		0.011	B
Vest4		0.13
MutPred		0.17		Loss of methylation at K174 (P = 0.0057)
MVP		0.26
MPC		0.41
ClinPred		0.10	T
GERP RS		-3.6
PromoterAI		-0.0053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.10
gMVP		0.18
Mutation Taster		=99/1	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

hg19: chr20-62369787;