17-38914449-C-T

Variant names:

• chr17-38914449-C-T
• NM_006148.4:c.482C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006148.4(LASP1):​c.482C>T​(p.Pro161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LASP1 NM_006148.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.511

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]

ACMG classification

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=0.11848658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LASP1	NM_006148.4	c.482C>T	p.Pro161Leu	missense_variant	Exon 5 of 7	ENST00000318008.11	NP_006139.1
LASP1	NM_001271608.2	c.314C>T	p.Pro105Leu	missense_variant	Exon 4 of 6		NP_001258537.1
LASP1	XM_047435965.1	c.374C>T	p.Pro125Leu	missense_variant	Exon 5 of 7		XP_047291921.1
LASP1	NR_073384.2	n.784C>T		non_coding_transcript_exon_variant	Exon 6 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LASP1	ENST00000318008.11	c.482C>T	p.Pro161Leu	missense_variant	Exon 5 of 7	1	NM_006148.4	ENSP00000325240.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.482C>T (p.P161L) 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 482, causing the proline (P) at amino acid position 161 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	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	.;T;T;T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.81	T;.;T;D;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;M;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.3	N;N;N;N;.
REVEL	Benign	0.075
Sift	Benign	0.049	D;D;D;D;.
Sift4G	Benign	0.10	T;T;T;D;D
Polyphen		0.020	.;B;B;.;.
Vest4		0.22
MutPred		0.26		.;Loss of phosphorylation at T166 (P = 0.1121);Loss of phosphorylation at T166 (P = 0.1121);.;.;
MVP		0.35
MPC		0.037
ClinPred		0.74	D
GERP RS		5.2
Varity_R		0.079
gMVP		0.59

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.

Other links and lift over

hg19: chr17-37070702;