Variant 13-46148354-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002298.5(LCP1):c.976C>T(p.Arg326Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,457,372 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

LCP1
NM_002298.5 missense, splice_region

Scores

Splicing: ADA: 0.04774

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25

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:

LCP1 (HGNC:):

LCP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCP1	NM_002298.5 linkuse as main transcript	c.976C>T	p.Arg326Trp	missense_variant, splice_region_variant	9/16	ENST00000323076.7	NP_002289.2	P13796-1A0A024RDT4
LCP1	XM_005266374.3 linkuse as main transcript	c.976C>T	p.Arg326Trp	missense_variant, splice_region_variant	9/16		XP_005266431.1	P13796-1A0A024RDT4
LCP1	XM_047430303.1 linkuse as main transcript	c.976C>T	p.Arg326Trp	missense_variant, splice_region_variant	9/16		XP_047286259.1
LCP1	XM_047430304.1 linkuse as main transcript	c.541C>T	p.Arg181Trp	missense_variant, splice_region_variant	7/14		XP_047286260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCP1	ENST00000323076.7 linkuse as main transcript	c.976C>T	p.Arg326Trp	missense_variant, splice_region_variant	9/16	1	NM_002298.5	ENSP00000315757.2		P13796-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250468

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135438

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1457372

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725306

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 08, 2024

The c.976C>T (p.R326W) alteration is located in exon 9 (coding exon 8) of the LCP1 gene. This alteration results from a C to T substitution at nucleotide position 976, causing the arginine (R) at amino acid position 326 to be replaced by a tryptophan (W). 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

0.18

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.88

D;D

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.88

LIST_S2

Pathogenic

0.99

.;D

M_CAP

Uncertain

0.25

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Uncertain

0.75

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.2

D;D

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;D

Vest4

0.44

MutPred

0.54

Gain of catalytic residue at L325 (P = 6e-04);Gain of catalytic residue at L325 (P = 6e-04);

MVP

0.86

MPC

0.96

ClinPred

0.58

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.25

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.048

dbscSNV1_RF

Benign

0.21

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over