17-38914461-C-T

Position:

chr17-38914461-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000318008.11(LASP1):c.494C>T(p.Pro165Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000747 in 1,606,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P165P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

LASP1
ENST00000318008.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

Variant links:

Genes affected

LASP1 (HGNC:6513): (LIM and SH3 protein 1) This gene encodes a member of a subfamily of LIM proteins, characterized by a LIM motif and a domain of Src homology region 3, and also a member of the nebulin family of actin-binding proteins. The encoded protein is a cAMP and cGMP dependent signaling protein and binds to the actin cytoskeleton at extensions of the cell membrane. The encoded protein has been linked to metastatic breast cancer, hematopoetic tumors such as B-cell lymphomas, and colorectal cancer. [provided by RefSeq, Oct 2012]

LASP1 links:

LASP1 (HGNC:):

LASP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12866244).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LASP1	NM_006148.4 linkuse as main transcript	c.494C>T	p.Pro165Leu	missense_variant	5/7	ENST00000318008.11	NP_006139.1	Q14847-1A0A024R1S8
LASP1	NM_001271608.2 linkuse as main transcript	c.326C>T	p.Pro109Leu	missense_variant	4/6		NP_001258537.1	Q14847-3B4DIC4
LASP1	XM_047435965.1 linkuse as main transcript	c.386C>T	p.Pro129Leu	missense_variant	5/7		XP_047291921.1
LASP1	NR_073384.2 linkuse as main transcript	n.796C>T		non_coding_transcript_exon_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LASP1	ENST00000318008.11 linkuse as main transcript	c.494C>T	p.Pro165Leu	missense_variant	5/7	1	NM_006148.4	ENSP00000325240.6		Q14847-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

242548

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131434

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.00000550

AC:

AN:

1454262

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

Feb 28, 2023

The c.494C>T (p.P165L) alteration is located in exon 5 (coding exon 5) of the LASP1 gene. This alteration results from a C to T substitution at nucleotide position 494, causing the proline (P) at amino acid position 165 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

.;T;T;T;.

Eigen

Benign

-0.013

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.75

T;.;T;T;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.13

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

.;M;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

N;D;D;D;.

REVEL

Benign

0.13

Sift

Uncertain

0.027

D;D;D;D;.

Sift4G

Uncertain

0.038

D;D;D;D;D

Polyphen

0.72

.;P;P;.;.

Vest4

0.33

MutPred

0.30

.;Gain of catalytic residue at P165 (P = 0.0393);Gain of catalytic residue at P165 (P = 0.0393);.;.;

MVP

0.32

MPC

0.038

ClinPred

0.61

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.30

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

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