rs199546311

Variant names:

• chr6-12749741-C-T
• rs199546311
• NM_030948.6:c.201C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_030948.6(PHACTR1):​c.201C>T​(p.Ser67Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,611,934 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0014 (6 hom.)
• Consequence: PHACTR1 NM_030948.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.130
• Publications: 1 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), G2P, Ambry Genetics
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000309066 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 6-12749741-C-T is Benign according to our data. Variant chr6-12749741-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656233.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.13 with no splicing effect.
• BS2: High AC in GnomAd4 at 205 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030948.6. 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
	PHACTR1	NM_030948.6	MANE Select	c.201C>T	p.Ser67Ser	synonymous	Exon 4 of 15	NP_112210.1	Q9C0D0-1
	PHACTR1	NM_001322310.2		c.201C>T	p.Ser67Ser	synonymous	Exon 2 of 14	NP_001309239.1
	PHACTR1	NM_001374581.2		c.201C>T	p.Ser67Ser	synonymous	Exon 3 of 13	NP_001361510.1	A0A6Q8PG87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	ENST00000332995.12	TSL:2 MANE Select	c.201C>T	p.Ser67Ser	synonymous	Exon 4 of 15	ENSP00000329880.8	Q9C0D0-1
	PHACTR1	ENST00000379348.3	TSL:1	n.378C>T		non_coding_transcript_exon	Exon 3 of 4
	PHACTR1	ENST00000674595.1		c.201C>T	p.Ser67Ser	synonymous	Exon 3 of 13	ENSP00000502157.1	A0A6Q8PG87

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 151638 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.00568

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00180

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.00134 AC: 323 AN: 241082 AF XY: 0.00143

Gnomad AFR exome AF: 0.0000678

Gnomad AMR exome AF: 0.000379

Gnomad ASJ exome AF: 0.00173

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00371

Gnomad NFE exome AF: 0.00169

Gnomad OTH exome AF: 0.00288

GnomAD4 exome AF: 0.00139 AC: 2024 AN: 1460188 Hom.: 6 Cov.: 33 AF XY: 0.00143 AC XY: 1036 AN XY: 726400

African (AFR) AF: 0.000418 AC: 14 AN: 33478

American (AMR) AF: 0.000492 AC: 22 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 36 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000661 AC: 57 AN: 86254

European-Finnish (FIN) AF: 0.00427 AC: 222 AN: 51994

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5764

European-Non Finnish (NFE) AF: 0.00143 AC: 1586 AN: 1111810

Other (OTH) AF: 0.00118 AC: 71 AN: 60348

GnomAD4 genome AF: 0.00135 AC: 205 AN: 151746 Hom.: 0 Cov.: 27 AF XY: 0.00154 AC XY: 114 AN XY: 74176

African (AFR) AF: 0.000193 AC: 8 AN: 41394

American (AMR) AF: 0.000458 AC: 7 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.000626 AC: 3 AN: 4796

European-Finnish (FIN) AF: 0.00568 AC: 60 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00180 AC: 122 AN: 67824

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.00154 Hom.: 2

Bravo AF: 0.00101

EpiCase AF: 0.00251

EpiControl AF: 0.00154

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PHACTR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		-0.13
PromoterAI		-0.086	Neutral
Mutation Taster		=96/4	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: rs199546311; hg19: chr6-12749973;