rs6070943

Variant names:

• chr20-59780936-G-A
• rs6070943
• NM_080672.5:c.1174+6446G>A

Variant summary

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

The NM_080672.5(PHACTR3):​c.1174+6446G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,086 control chromosomes in the GnomAD database, including 3,794 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 0.21 (3794 hom., cov: 33)
• Consequence: PHACTR3 NM_080672.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.82
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR3	NM_080672.5	c.1174+6446G>A		intron_variant	Intron 7 of 12	ENST00000371015.6	NP_542403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR3	ENST00000371015.6	c.1174+6446G>A		intron_variant	Intron 7 of 12	1	NM_080672.5	ENSP00000360054.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32177 AN: 151968 Hom.: 3785 Cov.: 33

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.212 AC: 32214 AN: 152086 Hom.: 3794 Cov.: 33 AF XY: 0.210 AC XY: 15639 AN XY: 74340

African (AFR) AF: 0.308 AC: 12765 AN: 41442

American (AMR) AF: 0.170 AC: 2608 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1322 AN: 5166

South Asian (SAS) AF: 0.177 AC: 853 AN: 4816

European-Finnish (FIN) AF: 0.149 AC: 1583 AN: 10594

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11851 AN: 67986

Other (OTH) AF: 0.205 AC: 433 AN: 2110

Alfa AF: 0.183 Hom.: 1385

Bravo AF: 0.220

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.078
DANN	Benign	0.78
PhyloP100		-4.8
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: rs6070943; hg19: chr20-58355991; COSMIC: COSV63025497;