3-142650997-G-A

Variant names:

• chr3-142650997-G-A
• rs6798232
• NM_001145319.2:c.-36-13205G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145319.2(PLS1):​c.-36-13205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,938 control chromosomes in the GnomAD database, including 30,090 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 0.62 (30090 hom., cov: 30)
• Consequence: PLS1 NM_001145319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 6 publications found

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]

ENSG00000287045 (HGNC:):

PLS1-AS1 (HGNC:40451): (PLS1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLS1	NM_001145319.2	c.-36-13205G>A		intron_variant	Intron 1 of 15	ENST00000457734.7	NP_001138791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLS1	ENST00000457734.7	c.-36-13205G>A		intron_variant	Intron 1 of 15	2	NM_001145319.2	ENSP00000387890.2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94825 AN: 151820 Hom.: 30059 Cov.: 30

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.625 AC: 94899 AN: 151938 Hom.: 30090 Cov.: 30 AF XY: 0.621 AC XY: 46099 AN XY: 74268

African (AFR) AF: 0.674 AC: 27920 AN: 41422

American (AMR) AF: 0.496 AC: 7572 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2048 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2004 AN: 5142

South Asian (SAS) AF: 0.455 AC: 2184 AN: 4804

European-Finnish (FIN) AF: 0.689 AC: 7271 AN: 10556

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43725 AN: 67962

Other (OTH) AF: 0.615 AC: 1300 AN: 2114

Alfa AF: 0.607 Hom.: 10806

Bravo AF: 0.613

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.34
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6798232; hg19: chr3-142369839;