chr20-59773348-C-A

Position:

• chr20-59773348-C-A

Variant summary

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

The NM_080672.5(PHACTR3):​c.821C>A​(p.Thr274Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T274I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PHACTR3 NM_080672.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.59

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR3	NM_080672.5	c.821C>A	p.Thr274Lys	missense_variant	6/13	ENST00000371015.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR3	ENST00000371015.6	c.821C>A	p.Thr274Lys	missense_variant	6/13	1	NM_080672.5	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jun 22, 2023

The c.821C>A (p.T274K) alteration is located in exon 6 (coding exon 6) of the PHACTR3 gene. This alteration results from a C to A substitution at nucleotide position 821, causing the threonine (T) at amino acid position 274 to be replaced by a lysine (K). 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	Uncertain	0.39
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	.;T;.;.;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D;D;.;.;D
M_CAP	Benign	0.0077	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	.;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.15	T;T;T;T;T;T
Sift4G	Benign	0.89	T;T;T;T;T;T
Polyphen		0.82, 0.99	.;P;.;.;.;D
Vest4		0.64
MutPred		0.30		.;Gain of ubiquitination at T274 (P = 0.0048);.;.;.;.;
MVP		0.28
MPC		0.41
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.20
gMVP		0.56

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: chr20-58348403;