3-142676111-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001145319.2(PLS1):c.365-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00799 in 1,566,386 control chromosomes in the GnomAD database, including 832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (443 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (389 hom.)
• Consequence: PLS1 NM_001145319.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0910

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-142676111-A-G is Benign according to our data. Variant chr3-142676111-A-G is described in ClinVar as [Benign]. Clinvar id is 1239682.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLS1	NM_001145319.2	c.365-46A>G		intron_variant		ENST00000457734.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLS1	ENST00000457734.7	c.365-46A>G		intron_variant		2	NM_001145319.2	P1
	ENST00000690164.1	n.119-18905T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6480 AN: 152214 Hom.: 439 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0296

GnomAD3 exomes AF: 0.0114 AC: 2641 AN: 231174 Hom.: 181 AF XY: 0.00842 AC XY: 1057 AN XY: 125464

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.00740

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000151

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000464

Gnomad OTH exome AF: 0.00437

GnomAD4 exome AF: 0.00426 AC: 6021 AN: 1414054 Hom.: 389 Cov.: 26 AF XY: 0.00366 AC XY: 2580 AN XY: 705466

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.00888

Gnomad4 ASJ exome AF: 0.000162

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000312

Gnomad4 OTH exome AF: 0.00936

GnomAD4 genome AF: 0.0427 AC: 6502 AN: 152332 Hom.: 443 Cov.: 32 AF XY: 0.0416 AC XY: 3099 AN XY: 74506

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0275 Hom.: 45

Bravo AF: 0.0488

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.5
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs16852550; hg19: chr3-142394953;