Genetic Variant NM_006148.4:c.316G>A (chr17-38898478-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_006148.4(LASP1):c.316G>A(p.Glu106Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000858 in 1,399,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

LASP1
NM_006148.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.92

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.822

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LASP1	NM_006148.4 link	c.316G>A	p.Glu106Lys	missense_variant	Exon 4 of 7	ENST00000318008.11	NP_006139.1	Q14847-1A0A024R1S8
LASP1	NM_001271608.2 link	c.148G>A	p.Glu50Lys	missense_variant	Exon 3 of 6		NP_001258537.1	Q14847-3B4DIC4
LASP1	XM_047435965.1 link	c.208G>A	p.Glu70Lys	missense_variant	Exon 4 of 7		XP_047291921.1
LASP1	NR_073384.2 link	n.618G>A		non_coding_transcript_exon_variant	Exon 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LASP1	ENST00000318008.11 link	c.316G>A	p.Glu106Lys	missense_variant	Exon 4 of 7	1	NM_006148.4	ENSP00000325240.6		Q14847-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000639

AC:

AN:

156488

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82322

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000858

AC:

AN:

1399274

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690162

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:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000927

Gnomad4 OTH exome

AF:

0.0000172

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 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.316G>A (p.E106K) alteration is located in exon 4 (coding exon 4) of the LASP1 gene. This alteration results from a G to A substitution at nucleotide position 316, causing the glutamic acid (E) at amino acid position 106 to be replaced by a lysine (K). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

.;T;T;T

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

D;.;D;D

M_CAP

Benign

0.053

MetaRNN

Pathogenic

0.82

D;D;D;D

MetaSVM

Benign

-0.36

MutationAssessor

Pathogenic

3.1

.;M;M;.

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Uncertain

0.36

Sift

Benign

0.14

T;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.68

MutPred

0.57

.;Gain of MoRF binding (P = 0.0022);Gain of MoRF binding (P = 0.0022);.;

MVP

0.79

MPC

2.8

ClinPred

0.99

GERP RS

5.4

Varity_R

0.83

gMVP

0.90

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