20-59824364-G-T

Variant names:

• chr20-59824364-G-T
• rs746219
• NM_080672.5:c.1329-12141G>T

Variant summary

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

The NM_080672.5(PHACTR3):​c.1329-12141G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 152,274 control chromosomes in the GnomAD database, including 423 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 0.051 (423 hom., cov: 32)
• Consequence: PHACTR3 NM_080672.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

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.1329-12141G>T		intron	N/A	NP_542403.1	Q96KR7-1
	PHACTR3	NM_001199505.1		c.1320-12141G>T		intron	N/A	NP_001186434.1	Q96KR7-4
	PHACTR3	NM_001199506.2		c.1206-12141G>T		intron	N/A	NP_001186435.1	Q96KR7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR3	ENST00000371015.6	TSL:1 MANE Select	c.1329-12141G>T		intron	N/A	ENSP00000360054.1	Q96KR7-1
	PHACTR3	ENST00000395636.6	TSL:1	c.1206-12141G>T		intron	N/A	ENSP00000378998.2	Q96KR7-2
	PHACTR3	ENST00000361300.4	TSL:1	c.996-12141G>T		intron	N/A	ENSP00000354555.4	Q96KR7-3

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7730 AN: 152156 Hom.: 422 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.0511

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

GnomAD4 genome AF: 0.0508 AC: 7736 AN: 152274 Hom.: 423 Cov.: 32 AF XY: 0.0558 AC XY: 4153 AN XY: 74448

African (AFR) AF: 0.0128 AC: 531 AN: 41570

American (AMR) AF: 0.127 AC: 1949 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 148 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1135 AN: 5152

South Asian (SAS) AF: 0.125 AC: 602 AN: 4826

European-Finnish (FIN) AF: 0.0465 AC: 493 AN: 10600

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0393 AC: 2671 AN: 68034

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0441 Hom.: 374

Bravo AF: 0.0553

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.58
PhyloP100		1.5
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: rs746219; hg19: chr20-58399419;