3-142664476-G-A

Position:

• chr3-142664476-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001145319.2(PLS1):​c.70+169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 152,002 control chromosomes in the GnomAD database, including 597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.079 (597 hom., cov: 32)
• Consequence: PLS1 NM_001145319.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.387

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 3-142664476-G-A is Benign according to our data. Variant chr3-142664476-G-A is described in ClinVar as [Benign]. Clinvar id is 1263995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLS1	NM_001145319.2	c.70+169G>A		intron_variant		ENST00000457734.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLS1	ENST00000457734.7	c.70+169G>A		intron_variant		2	NM_001145319.2	P1
	ENST00000690164.1	n.119-7270C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11947 AN: 151882 Hom.: 595 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0776

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0887

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

GnomAD4 genome AF: 0.0786 AC: 11945 AN: 152002 Hom.: 597 Cov.: 32 AF XY: 0.0765 AC XY: 5685 AN XY: 74302

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.0670

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.0790

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.0776

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.0900

Alfa AF: 0.0976 Hom.: 133

Bravo AF: 0.0749

Asia WGS AF: 0.0780 AC: 272 AN: 3474

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 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.75

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: rs2272150; hg19: chr3-142383318;