X-115561214-G-C

Position:

• chrX-115561214-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005032.7(PLS3):​c.-55G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.63 (15473 hom., 20861 hem., cov: 23)
  • Exomes 𝑓: 0.55 (6 hom. 16 hem.)
  • Failed GnomAD Quality Control
• Consequence: PLS3 NM_005032.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.872

Genes affected

PLS3 (HGNC:9091): (plastin 3) 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. Plastin 1 (otherwise known as Fimbrin) is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). The C-terminal 570 amino acids of the T-plastin and L-plastin proteins are 83% identical. It contains a potential calcium-binding site near the N terminus. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2010]

PLS3-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLS3	NM_005032.7	c.-55G>C		5_prime_UTR_variant	1/16	ENST00000355899.8	NP_005023.2
PLS3	NM_001282337.2	c.-240G>C		5_prime_UTR_variant	1/18		NP_001269266.1
PLS3-AS1	NR_110383.1	n.233+1190C>G		intron_variant
PLS3-AS1	NR_110384.1	n.233+1190C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLS3	ENST00000355899	c.-55G>C		5_prime_UTR_variant	1/16	1	NM_005032.7	ENSP00000348163.3

Frequencies

GnomAD3 genomes AF: 0.626 AC: 69487 AN: 111004 Hom.: 15466 Cov.: 23 AF XY: 0.626 AC XY: 20808 AN XY: 33224

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.624

GnomAD4 exome AF: 0.552 AC: 37 AN: 67 Hom.: 6 Cov.: 0 AF XY: 0.552 AC XY: 16 AN XY: 29

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.626 AC: 69544 AN: 111056 Hom.: 15473 Cov.: 23 AF XY: 0.627 AC XY: 20861 AN XY: 33286

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.626

Alfa AF: 0.406 Hom.: 1666

Bravo AF: 0.626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs757124; hg19: chrX-114795541;