chr20-59751377-A-G

Variant names:

• chr20-59751377-A-G
• rs864184
• NM_080672.5:c.358+3542A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080672.5(PHACTR3):​c.358+3542A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,018 control chromosomes in the GnomAD database, including 44,105 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44105 hom., cov: 32)
• Consequence: PHACTR3 NM_080672.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR3	NM_080672.5	c.358+3542A>G		intron_variant	Intron 3 of 12	ENST00000371015.6	NP_542403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR3	ENST00000371015.6	c.358+3542A>G		intron_variant	Intron 3 of 12	1	NM_080672.5	ENSP00000360054.1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115572 AN: 151900 Hom.: 44071 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.763

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.761 AC: 115657 AN: 152018 Hom.: 44105 Cov.: 32 AF XY: 0.761 AC XY: 56552 AN XY: 74312

African (AFR) AF: 0.739 AC: 30643 AN: 41446

American (AMR) AF: 0.787 AC: 12028 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2625 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3536 AN: 5138

South Asian (SAS) AF: 0.771 AC: 3717 AN: 4820

European-Finnish (FIN) AF: 0.794 AC: 8417 AN: 10596

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52140 AN: 67948

Other (OTH) AF: 0.765 AC: 1615 AN: 2112

Alfa AF: 0.768 Hom.: 91996

Bravo AF: 0.760

Asia WGS AF: 0.754 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.60
PhyloP100		-0.091
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs864184; hg19: chr20-58326432;