chrX-115610289-G-T

Variant names:

• chrX-115610289-G-T
• NM_005032.7:c.39G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005032.7(PLS3):​c.39G>T​(p.Glu13Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000942 in 1,061,125 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: PLS3 NM_005032.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18313953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLS3	NM_005032.7	c.39G>T	p.Glu13Asp	missense_variant	Exon 2 of 16	ENST00000355899.8	NP_005023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLS3	ENST00000355899.8	c.39G>T	p.Glu13Asp	missense_variant	Exon 2 of 16	1	NM_005032.7	ENSP00000348163.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.42e-7 AC: 1 AN: 1061125 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 333451

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000122

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.66
DEOGEN2	Benign	0.017	T;T;T;.
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.87	D;.;D;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;M;M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.59	.;N;.;.
REVEL	Benign	0.21
Sift	Benign	0.39	.;T;.;.
Sift4G	Benign	0.41	.;T;T;T
Polyphen		0.0010	.;B;B;.
Vest4		0.53
MutPred		0.44		Loss of methylation at K11 (P = 0.0923);Loss of methylation at K11 (P = 0.0923);Loss of methylation at K11 (P = 0.0923);Loss of methylation at K11 (P = 0.0923);
MVP		0.88
ClinPred		0.12	T
GERP RS		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.18
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-114844601;