Genetic Variant LASP1:p.Glu106Lys (chr17-38898478-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.822

BS2

High AC in GnomAdExome4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006148.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LASP1	NM_006148.4	MANE Select	c.316G>A	p.Glu106Lys	missense	Exon 4 of 7	NP_006139.1	Q14847-1
LASP1	NM_001271608.2		c.148G>A	p.Glu50Lys	missense	Exon 3 of 6	NP_001258537.1	Q14847-3
LASP1	NR_073384.2		n.618G>A		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LASP1	ENST00000318008.11	TSL:1 MANE Select	c.316G>A	p.Glu106Lys	missense	Exon 4 of 7	ENSP00000325240.6	Q14847-1
LASP1	ENST00000443937.7	TSL:1	n.*210G>A		non_coding_transcript_exon	Exon 5 of 8	ENSP00000414803.3	F6S2S5
LASP1	ENST00000443937.7	TSL:1	n.*210G>A		3_prime_UTR	Exon 5 of 8	ENSP00000414803.3	F6S2S5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000639

AC:

AN:

156488

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

31596

American (AMR)

AF:

0.00

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00000927

AC:

AN:

1078868

Other (OTH)

AF:

0.0000172

AC:

AN:

57996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.053

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.36

MutationAssessor

Pathogenic

3.1

PhyloP100

9.9

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.36

Sift

Benign

0.14

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.68

MutPred

0.57

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

Mutation Taster

=12/88

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over