13-46134155-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002298.5(LCP1):c.1598A>G(p.Lys533Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K533E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LCP1
NM_002298.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.150

Variant links:

Genes affected

LCP1 (HGNC:6528): (lymphocyte cytosolic protein 1) Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. Plastin 1 (otherwise known as Fimbrin) is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). However, L-plastin has been found in many types of malignant human cells of non-hemopoietic origin suggesting that its expression is induced accompanying tumorigenesis in solid tissues. [provided by RefSeq, Jul 2008]

LCP1 links:

CPB2-AS1 (HGNC:39898): (CPB2 antisense RNA 1)

CPB2-AS1 links:

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ACMG classification

Classification made for transcript

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=0.142497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP1	NM_002298.5 link	c.1598A>G	p.Lys533Arg	missense_variant	Exon 14 of 16	ENST00000323076.7	NP_002289.2	P13796-1A0A024RDT4
LCP1	XM_005266374.3 link	c.1598A>G	p.Lys533Arg	missense_variant	Exon 14 of 16		XP_005266431.1	P13796-1A0A024RDT4
LCP1	XM_047430303.1 link	c.1598A>G	p.Lys533Arg	missense_variant	Exon 14 of 16		XP_047286259.1
LCP1	XM_047430304.1 link	c.1163A>G	p.Lys388Arg	missense_variant	Exon 12 of 14		XP_047286260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LCP1	ENST00000323076.7 link	c.1598A>G	p.Lys533Arg	missense_variant	Exon 14 of 16	1	NM_002298.5	ENSP00000315757.2	P13796-1
LCP1	ENST00000398576.6 link	c.1598A>G	p.Lys533Arg	missense_variant	Exon 17 of 19	5		ENSP00000381581.1	P13796-1
LCP1	ENST00000674665.1 link	c.305A>G	p.Lys102Arg	missense_variant	Exon 3 of 5			ENSP00000501964.1	P13796-2
CPB2-AS1	ENST00000663159.1 link	n.470-17339T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461476

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727066

show subpopulations

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:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1598A>G (p.K533R) alteration is located in exon 14 (coding exon 13) of the LCP1 gene. This alteration results from a A to G substitution at nucleotide position 1598, causing the lysine (K) at amino acid position 533 to be replaced by an arginine (R). 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

0.073

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

7.7

DANN

Benign

0.89

DEOGEN2

Uncertain

0.49

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.47

.;T

M_CAP

Benign

0.078

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.60

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.25

N;N

REVEL

Benign

0.21

Sift

Benign

0.043

D;D

Sift4G

Uncertain

0.035

D;D

Polyphen

0.0

B;B

Vest4

0.049

MutPred

0.39

Loss of ubiquitination at K533 (P = 0.0134);Loss of ubiquitination at K533 (P = 0.0134);

MVP

0.61

MPC

0.29

ClinPred

0.11

GERP RS

-5.5

Varity_R

0.099

gMVP

0.37

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over