20-59605045-C-G

Variant names:

• chr20-59605045-C-G
• NM_080672.5:c.31C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/21 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13508716).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080672.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR3	NM_080672.5	MANE Select	c.31C>G	p.Leu11Val	missense	Exon 1 of 13	NP_542403.1	Q96KR7-1
	PHACTR3	NM_001199505.1		c.109+27428C>G		intron	N/A	NP_001186434.1	Q96KR7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR3	ENST00000371015.6	TSL:1 MANE Select	c.31C>G	p.Leu11Val	missense	Exon 1 of 13	ENSP00000360054.1	Q96KR7-1
	PHACTR3	ENST00000908180.1		c.31C>G	p.Leu11Val	missense	Exon 1 of 12	ENSP00000578239.1
	PHACTR3	ENST00000908181.1		c.31C>G	p.Leu11Val	missense	Exon 1 of 11	ENSP00000578240.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.080
Sift	Benign	0.054	T
Sift4G	Benign	0.093	T
Polyphen		0.39	B
Vest4		0.20
MutPred		0.15		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
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

hg19: chr20-58180100;