chr17-38914382-A-T

Variant names:

• chr17-38914382-A-T
• rs151189344
• NM_006148.4:c.415A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006148.4(LASP1):​c.415A>T​(p.Met139Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LASP1 NM_006148.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022361666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LASP1	NM_006148.4	c.415A>T	p.Met139Leu	missense_variant	Exon 5 of 7	ENST00000318008.11	NP_006139.1
LASP1	NM_001271608.2	c.247A>T	p.Met83Leu	missense_variant	Exon 4 of 6		NP_001258537.1
LASP1	XM_047435965.1	c.307A>T	p.Met103Leu	missense_variant	Exon 5 of 7		XP_047291921.1
LASP1	NR_073384.2	n.717A>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.415A>T	p.Met139Leu	missense_variant	Exon 5 of 7	1	NM_006148.4	ENSP00000325240.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.0040
DANN	Benign	0.83
DEOGEN2	Benign	0.084	.;T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.47	T;.;T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.022	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	.;N;N;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.030	N;N;N;N
REVEL	Benign	0.028
Sift	Benign	0.58	T;T;T;T
Sift4G	Benign	0.74	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.14
MutPred		0.31		.;Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);.;
MVP		0.38
MPC		0.035
ClinPred		0.070	T
GERP RS		-11
Varity_R		0.085
gMVP		0.14

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

Other links and lift over

dbSNP: rs151189344; hg19: chr17-37070635;