rs368361108

Variant names:

• chr20-59755238-C-T
• rs368361108
• NM_080672.5:c.415C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-59755238-C-T
• chr20-59755238-C-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_080672.5(PHACTR3):​c.415C>T​(p.Pro139Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: PHACTR3 NM_080672.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.055404156).
• BS2: High AC in GnomAd4 at 15 AD gene.

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.415C>T	p.Pro139Ser	missense	Exon 4 of 13	NP_542403.1	Q96KR7-1
	PHACTR3	NM_001199505.1		c.406C>T	p.Pro136Ser	missense	Exon 4 of 13	NP_001186434.1	Q96KR7-4
	PHACTR3	NM_001199506.2		c.292C>T	p.Pro98Ser	missense	Exon 4 of 13	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.415C>T	p.Pro139Ser	missense	Exon 4 of 13	ENSP00000360054.1	Q96KR7-1
	PHACTR3	ENST00000395636.6	TSL:1	c.292C>T	p.Pro98Ser	missense	Exon 4 of 13	ENSP00000378998.2	Q96KR7-2
	PHACTR3	ENST00000361300.4	TSL:1	c.292C>T	p.Pro98Ser	missense	Exon 4 of 12	ENSP00000354555.4	Q96KR7-3

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152236 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: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000765 AC: 19 AN: 248452 AF XY: 0.0000966

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000989

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000664 AC: 97 AN: 1461606 Hom.: 0 Cov.: 31 AF XY: 0.0000825 AC XY: 60 AN XY: 727134

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000585 AC: 65 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000678 Hom.: 0

Bravo AF: 0.0000793

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.26
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.9
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.016
Sift	Benign	0.49	T
Sift4G	Benign	0.80	T
Polyphen		0.0060	B
Vest4		0.27
MVP		0.13
MPC		0.078
ClinPred		0.080	T
GERP RS		2.6
Varity_R		0.050
gMVP		0.18
Mutation Taster		=91/9	polymorphism

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: rs368361108; hg19: chr20-58330293;