NM_002298.5:c.1122C>A

Variant names:

• chr13-46146960-G-T
• NM_002298.5:c.1122C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_002298.5(LCP1):​c.1122C>A​(p.Tyr374*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCP1 NM_002298.5 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.29

Genes affected

LCP1 (HGNC:6528): (lymphocyte cytosolic protein 1) Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. Plastin 1 (otherwise known as Fimbrin) is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). However, L-plastin has been found in many types of malignant human cells of non-hemopoietic origin suggesting that its expression is induced accompanying tumorigenesis in solid tissues. [provided by RefSeq, Jul 2008]

CPB2-AS1 (HGNC:39898): (CPB2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-46146960-G-T is Pathogenic according to our data. Variant chr13-46146960-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 981804.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP1	NM_002298.5	c.1122C>A	p.Tyr374*	stop_gained	Exon 10 of 16	ENST00000323076.7	NP_002289.2
LCP1	XM_005266374.3	c.1122C>A	p.Tyr374*	stop_gained	Exon 10 of 16		XP_005266431.1
LCP1	XM_047430303.1	c.1122C>A	p.Tyr374*	stop_gained	Exon 10 of 16		XP_047286259.1
LCP1	XM_047430304.1	c.687C>A	p.Tyr229*	stop_gained	Exon 8 of 14		XP_047286260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP1	ENST00000323076.7	c.1122C>A	p.Tyr374*	stop_gained	Exon 10 of 16	1	NM_002298.5	ENSP00000315757.2
LCP1	ENST00000398576.6	c.1122C>A	p.Tyr374*	stop_gained	Exon 13 of 19	5		ENSP00000381581.1
LCP1	ENST00000469227.5	n.676C>A		non_coding_transcript_exon_variant	Exon 5 of 5	3
CPB2-AS1	ENST00000663159.1	n.470-4534G>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary breast ovarian cancer syndrome Pathogenic:1

Aug 01, 2020

Molecular Oncology Research Center, Barretos Cancer Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.93	D
Vest4		0.95
GERP RS		3.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr13-46721095;