rs6026990

Variant names:

• chr20-59602560-T-A
• rs6026990
• NM_001199505.1:c.109+24943T>A

Variant summary

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

The NM_001199505.1(PHACTR3):​c.109+24943T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,854 control chromosomes in the GnomAD database, including 3,046 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 0.16 (3046 hom., cov: 32)
• Consequence: PHACTR3 NM_001199505.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• Publications: 9 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 = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR3	NM_001199505.1	c.109+24943T>A		intron_variant	Intron 1 of 12		NP_001186434.1
PHACTR3	XM_011528525.3	c.-6+18872T>A		intron_variant	Intron 1 of 12		XP_011526827.1
PHACTR3	XM_017027626.3	c.-6+23107T>A		intron_variant	Intron 1 of 12		XP_016883115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR3	ENST00000359926.7	c.109+24943T>A		intron_variant	Intron 1 of 12	2		ENSP00000353002.3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23959 AN: 151740 Hom.: 3025 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0600

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.158 AC: 24016 AN: 151854 Hom.: 3046 Cov.: 32 AF XY: 0.159 AC XY: 11766 AN XY: 74182

African (AFR) AF: 0.329 AC: 13605 AN: 41398

American (AMR) AF: 0.142 AC: 2160 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 218 AN: 3468

East Asian (EAS) AF: 0.332 AC: 1713 AN: 5156

South Asian (SAS) AF: 0.190 AC: 913 AN: 4804

European-Finnish (FIN) AF: 0.0600 AC: 630 AN: 10498

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.0637 AC: 4329 AN: 67956

Other (OTH) AF: 0.154 AC: 324 AN: 2106

Alfa AF: 0.0912 Hom.: 620

Bravo AF: 0.173

Asia WGS AF: 0.240 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.38
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6026990; hg19: chr20-58177615; COSMIC: COSV107457470; COSMIC: COSV107457470;