NM_017806.4:c.520A>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/20 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

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=0.07219702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIME1	NM_017806.4	c.520A>C	p.Lys174Gln	missense_variant	Exon 5 of 6	ENST00000309546.8	NP_060276.2
LIME1	NM_001305654.2	c.485A>C	p.Gln162Pro	missense_variant	Exon 5 of 6		NP_001292583.1
LIME1	NM_001305655.2	c.485A>C	p.Gln162Pro	missense_variant	Exon 5 of 6		NP_001292584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIME1	ENST00000309546.8	c.520A>C	p.Lys174Gln	missense_variant	Exon 5 of 6	1	NM_017806.4	ENSP00000309521.3
ENSG00000273154	ENST00000632538.1	c.824A>C	p.Gln275Pro	missense_variant	Exon 6 of 6	3		ENSP00000488802.1
ENSG00000273047	ENST00000467211.1	c.163A>C	p.Lys55Gln	missense_variant	Exon 1 of 2	3		ENSP00000477118.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.520A>C (p.K174Q) alteration is located in exon 5 (coding exon 4) of the LIME1 gene. This alteration results from a A to C substitution at nucleotide position 520, causing the lysine (K) at amino acid position 174 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.037
Sift	Benign	0.16	T;.
Sift4G	Benign	0.26	T;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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.10
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-62369787;