chr20-59577527-G-C

Variant names:

• chr20-59577527-G-C
• rs961562111
• NM_001199505.1:c.19G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001199505.1(PHACTR3):​c.19G>C​(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000519 in 1,156,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G7W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: PHACTR3 NM_001199505.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16504085).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199505.1. 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_001199505.1		c.19G>C	p.Gly7Arg	missense	Exon 1 of 13	NP_001186434.1	Q96KR7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR3	ENST00000359926.7	TSL:2	c.19G>C	p.Gly7Arg	missense	Exon 1 of 13	ENSP00000353002.3	Q96KR7-4
	PHACTR3	ENST00000944653.1		c.-373G>C		5_prime_UTR	Exon 1 of 11	ENSP00000614712.1

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 4 AN: 149480 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000596

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000199 AC: 2 AN: 1007500 Hom.: 0 Cov.: 30 AF XY: 0.00000421 AC XY: 2 AN XY: 474562

African (AFR) AF: 0.00 AC: 0 AN: 20316

American (AMR) AF: 0.00 AC: 0 AN: 5892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11094

East Asian (EAS) AF: 0.00 AC: 0 AN: 19708

South Asian (SAS) AF: 0.00 AC: 0 AN: 18906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2500

European-Non Finnish (NFE) AF: 0.00000229 AC: 2 AN: 873736

Other (OTH) AF: 0.00 AC: 0 AN: 38250

GnomAD4 genome AF: 0.0000268 AC: 4 AN: 149480 Hom.: 0 Cov.: 33 AF XY: 0.0000274 AC XY: 2 AN XY: 72884

African (AFR) AF: 0.00 AC: 0 AN: 41150

American (AMR) AF: 0.00 AC: 0 AN: 15028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000596 AC: 4 AN: 67070

Other (OTH) AF: 0.00 AC: 0 AN: 2058

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.69
PROVEAN	Benign	0.35	N
REVEL	Benign	0.028
Sift	Uncertain	0.012	D
Sift4G	Benign	0.16	T
Vest4		0.24
MutPred		0.35		Gain of methylation at G7 (P = 0.005)
MVP		0.15
ClinPred		0.12	T
GERP RS		1.5
PromoterAI		0.23	Neutral
Mutation Taster		=96/4	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs961562111; hg19: chr20-58152582;