chr20-59605045-C-G

Position:

• chr20-59605045-C-G

Variant summary

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

The NM_080672.5(PHACTR3):​c.31C>G​(p.Leu11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PHACTR3 NM_080672.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94

Genes affected

PHACTR3 (HGNC:15833): (phosphatase and actin regulator 3) This gene encodes a member of the phosphatase and actin regulator protein family. The encoded protein is associated with the nuclear scaffold in proliferating cells, and binds to actin and the catalytic subunit of protein phosphatase-1, suggesting that it functions as a regulatory subunit of protein phosphatase-1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

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=0.13508716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR3	NM_080672.5	c.31C>G	p.Leu11Val	missense_variant	1/13	ENST00000371015.6	NP_542403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR3	ENST00000371015.6	c.31C>G	p.Leu11Val	missense_variant	1/13	1	NM_080672.5	ENSP00000360054	A1
PHACTR3	ENST00000434923.1	c.31C>G	p.Leu11Val	missense_variant	3/4	5		ENSP00000390915
PHACTR3	ENST00000359926.7	c.109+27428C>G		intron_variant		2		ENSP00000353002

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.31C>G (p.L11V) alteration is located in exon 1 (coding exon 1) of the PHACTR3 gene. This alteration results from a C to G substitution at nucleotide position 31, causing the leucine (L) at amino acid position 11 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.011	.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.53	T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.080
Sift	Benign	0.054	T;T
Sift4G	Benign	0.093	T;T
Polyphen		0.39	.;B
Vest4		0.20
MutPred		0.15		Loss of catalytic residue at L11 (P = 0.0456);Loss of catalytic residue at L11 (P = 0.0456);
MVP		0.13
MPC		0.094
ClinPred		0.27	T
GERP RS		3.3
Varity_R		0.092
gMVP		0.15

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: chr20-58180100;