3-142610077-C-G

Position:

• chr3-142610077-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145319.2(PLS1):​c.-37+13568C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,126 control chromosomes in the GnomAD database, including 4,581 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4581 hom., cov: 32)
• Consequence: PLS1 NM_001145319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516

Genes affected

PLS1 (HGNC:9090): (plastin 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. The protein encoded by this gene is a third distinct plastin isoform, which is specifically expressed at high levels in the small intestine. Alternatively spliced transcript variants varying in the 5' UTR, but encoding the same protein, have been found for this gene. A pseudogene of this gene is found on chromosome 11.[provided by RefSeq, Feb 2010]

PLS1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLS1	NM_001145319.2	c.-37+13568C>G		intron_variant		ENST00000457734.7	NP_001138791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLS1	ENST00000457734.7	c.-37+13568C>G		intron_variant		2	NM_001145319.2	ENSP00000387890.2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33246 AN: 152008 Hom.: 4566 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.196

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.219 AC: 33295 AN: 152126 Hom.: 4581 Cov.: 32 AF XY: 0.214 AC XY: 15889 AN XY: 74390

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.198

Alfa AF: 0.192 Hom.: 410

Bravo AF: 0.225

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.65

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: rs9826463; hg19: chr3-142328919;