3-142712158-G-C

Variant names:

• chr3-142712158-G-C
• rs3773506
• NM_001145319.2:c.*151G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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]

PLS1 Gene-Disease associations (from GenCC):

• hearing loss, autosomal dominant 76

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287045 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145319.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLS1	NM_001145319.2	MANE Select	c.*151G>C		3_prime_UTR	Exon 16 of 16	NP_001138791.1
	PLS1	NM_001172312.2		c.*151G>C		3_prime_UTR	Exon 16 of 16	NP_001165783.1
	PLS1	NM_002670.3		c.*151G>C		3_prime_UTR	Exon 16 of 16	NP_002661.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLS1	ENST00000457734.7	TSL:2 MANE Select	c.*151G>C		3_prime_UTR	Exon 16 of 16	ENSP00000387890.2
	PLS1	ENST00000337777.7	TSL:1	c.*151G>C		3_prime_UTR	Exon 16 of 16	ENSP00000336831.3
	ENSG00000287045	ENST00000664914.1		n.52+11672C>G		intron	N/A

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

African (AFR) AF: 0.167 AC: 2231 AN: 13396

American (AMR) AF: 0.0580 AC: 1035 AN: 17860

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 522 AN: 13306

East Asian (EAS) AF: 0.109 AC: 3310 AN: 30372

South Asian (SAS) AF: 0.0665 AC: 2263 AN: 34006

European-Finnish (FIN) AF: 0.0224 AC: 666 AN: 29720

Middle Eastern (MID) AF: 0.0531 AC: 120 AN: 2260

European-Non Finnish (NFE) AF: 0.0424 AC: 13661 AN: 321984

Other (OTH) AF: 0.0605 AC: 1616 AN: 26690

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

African (AFR) AF: 0.160 AC: 6623 AN: 41482

American (AMR) AF: 0.0502 AC: 767 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3466

East Asian (EAS) AF: 0.142 AC: 737 AN: 5186

South Asian (SAS) AF: 0.0621 AC: 299 AN: 4818

European-Finnish (FIN) AF: 0.0198 AC: 210 AN: 10604

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0415 AC: 2823 AN: 67986

Other (OTH) AF: 0.0592 AC: 125 AN: 2112

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.7
DANN	Benign	0.79
PhyloP100		0.84
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: rs3773506; hg19: chr3-142431000;