rs3773506

Positions:

• chr3-142712158-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001145319.2(PLS1):​c.*151G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 641,740 control chromosomes in the GnomAD database, including 1,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (687 hom., cov: 32)
  • Exomes 𝑓: 0.052 (929 hom.)
• Consequence: PLS1 NM_001145319.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.842

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 3-142712158-G-C is Benign according to our data. Variant chr3-142712158-G-C is described in ClinVar as [Benign]. Clinvar id is 1249967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLS1	NM_001145319.2	c.*151G>C		3_prime_UTR_variant	16/16	ENST00000457734.7	NP_001138791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLS1	ENST00000457734.7	c.*151G>C		3_prime_UTR_variant	16/16	2	NM_001145319.2	ENSP00000387890	P1
PLS1	ENST00000337777.7	c.*151G>C		3_prime_UTR_variant	16/16	1		ENSP00000336831	P1
	ENST00000690164.1	n.118+11672C>G		intron_variant, non_coding_transcript_variant
	ENST00000664914.1	n.52+11672C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11749 AN: 152028 Hom.: 688 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0598

GnomAD4 exome AF: 0.0519 AC: 25424 AN: 489594 Hom.: 929 Cov.: 6 AF XY: 0.0519 AC XY: 13171 AN XY: 253546

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.0580

Gnomad4 ASJ exome AF: 0.0392

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.0665

Gnomad4 FIN exome AF: 0.0224

Gnomad4 NFE exome AF: 0.0424

Gnomad4 OTH exome AF: 0.0605

GnomAD4 genome AF: 0.0773 AC: 11754 AN: 152146 Hom.: 687 Cov.: 32 AF XY: 0.0746 AC XY: 5546 AN XY: 74384

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0502

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0621

Gnomad4 FIN AF: 0.0198

Gnomad4 NFE AF: 0.0415

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0633 Hom.: 63

Bravo AF: 0.0839

Asia WGS AF: 0.0940 AC: 327 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.7
DANN	Benign	0.79

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: rs3773506; hg19: chr3-142431000;