NM_005032.7:c.87C>A

Variant names:

• chrX-115622259-C-A
• NM_005032.7:c.87C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_005032.7(PLS3):​c.87C>A​(p.Asn29Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000923 in 1,083,945 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: PLS3 NM_005032.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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 4 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity PLST_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLS3	NM_005032.7	c.87C>A	p.Asn29Lys	missense_variant	Exon 3 of 16	ENST00000355899.8	NP_005023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLS3	ENST00000355899.8	c.87C>A	p.Asn29Lys	missense_variant	Exon 3 of 16	1	NM_005032.7	ENSP00000348163.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.23e-7 AC: 1 AN: 1083945 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 351465

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: 0.00000120

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	Pathogenic	0.75
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D;.;D;.;T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.94	.;D;D;D;D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.53	D;D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.5	M;.;M;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.3	N;.;.;.;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.014	D;.;.;.;.
Sift4G	Benign	0.95	T;T;T;D;T
Polyphen		0.49	P;.;P;.;.
Vest4		0.36
MutPred		0.56		Gain of ubiquitination at N29 (P = 0.0198);.;Gain of ubiquitination at N29 (P = 0.0198);Gain of ubiquitination at N29 (P = 0.0198);.;
MVP		0.70
MPC		1.4
ClinPred		0.96	D
GERP RS		1.6
Varity_R		0.44
gMVP		0.80

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-114856571;