rs6027005

Variant names:

• chr20-59624163-C-T
• rs6027005
• NM_080672.5:c.118+19031C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000371015.6(PHACTR3):​c.118+19031C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0375 in 152,070 control chromosomes in the GnomAD database, including 122 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 0.038 (122 hom., cov: 32)
• Consequence: PHACTR3 ENST00000371015.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 3 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=-0.99).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0375 (5707/152070) while in subpopulation AFR AF = 0.0421 (1746/41482). AF 95% confidence interval is 0.0406. There are 122 homozygotes in GnomAd4. There are 2651 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5707 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371015.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR3	NM_080672.5	MANE Select	c.118+19031C>T		intron	N/A	NP_542403.1
	PHACTR3	NM_001199505.1		c.109+46546C>T		intron	N/A	NP_001186434.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR3	ENST00000371015.6	TSL:1 MANE Select	c.118+19031C>T		intron	N/A	ENSP00000360054.1
	PHACTR3	ENST00000359926.7	TSL:2	c.109+46546C>T		intron	N/A	ENSP00000353002.3
	PHACTR3	ENST00000434923.1	TSL:5	c.118+19031C>T		intron	N/A	ENSP00000390915.1

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5706 AN: 151950 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0288

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0419

Gnomad OTH AF: 0.0441

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

GnomAD4 genome AF: 0.0375 AC: 5707 AN: 152070 Hom.: 122 Cov.: 32 AF XY: 0.0357 AC XY: 2651 AN XY: 74344

African (AFR) AF: 0.0421 AC: 1746 AN: 41482

American (AMR) AF: 0.0288 AC: 440 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5148

South Asian (SAS) AF: 0.0199 AC: 96 AN: 4820

European-Finnish (FIN) AF: 0.0288 AC: 305 AN: 10594

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0419 AC: 2847 AN: 67964

Other (OTH) AF: 0.0431 AC: 91 AN: 2110

Alfa AF: 0.0456 Hom.: 34

Bravo AF: 0.0381

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.54
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6027005; hg19: chr20-58199218;