X-115588425-T-C

Variant names:

• chrX-115588425-T-C
• rs2522188
• NM_005032.7:c.-8-21818T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005032.7(PLS3):​c.-8-21818T>C variant causes a intron 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 0.68 (18741 hom., 22842 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: PLS3 NM_005032.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLS3	NM_005032.7	c.-8-21818T>C		intron_variant	Intron 1 of 15	ENST00000355899.8	NP_005023.2
PLS3	NM_001282337.2	c.-193-21818T>C		intron_variant	Intron 1 of 17		NP_001269266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLS3	ENST00000355899.8	c.-8-21818T>C		intron_variant	Intron 1 of 15	1	NM_005032.7	ENSP00000348163.3
PLS3	ENST00000489283.5	n.-8-21818T>C		intron_variant	Intron 1 of 5	1		ENSP00000420458.1
PLS3	ENST00000289290.7	c.-193-21818T>C		intron_variant	Intron 1 of 17	2		ENSP00000289290.4
PLS3	ENST00000626746.2	c.-8-21818T>C		intron_variant	Intron 1 of 2	4		ENSP00000487343.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 75843 AN: 111175 Hom.: 18733 Cov.: 24

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.651

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.682 AC: 75902 AN: 111225 Hom.: 18741 Cov.: 24 AF XY: 0.683 AC XY: 22842 AN XY: 33451

Gnomad4 AFR AF: 0.860 AC: 0.860443 AN: 0.860443

Gnomad4 AMR AF: 0.607 AC: 0.606989 AN: 0.606989

Gnomad4 ASJ AF: 0.631 AC: 0.63088 AN: 0.63088

Gnomad4 EAS AF: 0.454 AC: 0.453541 AN: 0.453541

Gnomad4 SAS AF: 0.706 AC: 0.706061 AN: 0.706061

Gnomad4 FIN AF: 0.714 AC: 0.714407 AN: 0.714407

Gnomad4 NFE AF: 0.614 AC: 0.614311 AN: 0.614311

Gnomad4 OTH AF: 0.653 AC: 0.653129 AN: 0.653129

Alfa AF: 0.634 Hom.: 36992

Bravo AF: 0.681

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2522188; hg19: chrX-114822737;