chr18-45992129-C-A

Variant names:

• chr18-45992129-C-A
• rs760686151
• NM_024430.4:c.815G>T

Variant summary

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

The NM_024430.4(PSTPIP2):​c.815G>T​(p.Arg272Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R272H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSTPIP2 NM_024430.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

Genes affected

PSTPIP2 (HGNC:9581): (proline-serine-threonine phosphatase interacting protein 2) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament polymerization. Predicted to be located in cytoskeleton and membrane. Predicted to be active in actin filament; cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSTPIP2	NM_024430.4	c.815G>T	p.Arg272Leu	missense_variant	Exon 11 of 15	ENST00000409746.5	NP_077748.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSTPIP2	ENST00000409746.5	c.815G>T	p.Arg272Leu	missense_variant	Exon 11 of 15	1	NM_024430.4	ENSP00000387261.4
PSTPIP2	ENST00000589328.5	c.742-146G>T		intron_variant	Intron 10 of 13	1		ENSP00000468622.1
PSTPIP2	ENST00000593086.1	n.444G>T		non_coding_transcript_exon_variant	Exon 2 of 3	3
PSTPIP2	ENST00000588801.5	n.657+6665G>T		intron_variant	Intron 8 of 8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.4
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.015	D
Polyphen		0.80	P
Vest4		0.64
MutPred		0.55		Loss of disorder (P = 0.0899);
MVP		0.63
MPC		0.93
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.83
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs760686151; hg19: chr18-43572095;