rs3773506

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-142712158-G-A
• chr3-142712158-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145319.2(PLS1):​c.*151G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000204 in 489,834 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: PLS1 NM_001145319.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.842
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLS1	NM_001145319.2	c.*151G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000457734.7	NP_001138791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLS1	ENST00000457734.7	c.*151G>A		3_prime_UTR_variant	Exon 16 of 16	2	NM_001145319.2	ENSP00000387890.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000204 AC: 1 AN: 489834 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 253674

African (AFR) AF: 0.00 AC: 0 AN: 13408

American (AMR) AF: 0.00 AC: 0 AN: 17866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13308

East Asian (EAS) AF: 0.00 AC: 0 AN: 30388

South Asian (SAS) AF: 0.00 AC: 0 AN: 34044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2262

European-Non Finnish (NFE) AF: 0.00000310 AC: 1 AN: 322122

Other (OTH) AF: 0.00 AC: 0 AN: 26708

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.1
DANN	Benign	0.69
PhyloP100		0.84

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;