rs10485363

Variant names:

• chr6-13137533-G-T
• rs10485363
• NM_030948.6:c.416-22671G>T

Variant summary

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

The NM_030948.6(PHACTR1):​c.416-22671G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,228 control chromosomes in the GnomAD database, including 1,730 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 0.14 (1730 hom., cov: 33)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611
• Publications: 7 publications found

Genes affected

PHACTR1 (HGNC:20990): (phosphatase and actin regulator 1) The protein encoded by this gene is a member of the phosphatase and actin regulator family of proteins. This family member can bind actin and regulate the reorganization of the actin cytoskeleton. It plays a role in tubule formation and in endothelial cell survival. Polymorphisms in this gene are associated with susceptibility to myocardial infarction, coronary artery disease and cervical artery dissection. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]

PHACTR1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 70

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000303958 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.416-22671G>T		intron_variant	Intron 5 of 14	ENST00000332995.12	NP_112210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12	c.416-22671G>T		intron_variant	Intron 5 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21308 AN: 152110 Hom.: 1730 Cov.: 33

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.140 AC: 21311 AN: 152228 Hom.: 1730 Cov.: 33 AF XY: 0.138 AC XY: 10240 AN XY: 74420

African (AFR) AF: 0.0889 AC: 3696 AN: 41558

American (AMR) AF: 0.174 AC: 2659 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3472

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5180

South Asian (SAS) AF: 0.0538 AC: 260 AN: 4834

European-Finnish (FIN) AF: 0.155 AC: 1643 AN: 10580

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11772 AN: 67986

Other (OTH) AF: 0.170 AC: 358 AN: 2110

Alfa AF: 0.164 Hom.: 2825

Bravo AF: 0.143

Asia WGS AF: 0.0420 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.79
DANN	Benign	0.45
PhyloP100		0.61
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: rs10485363; hg19: chr6-13137765;