chr6-13053411-C-T

Variant names:

• chr6-13053411-C-T
• rs141282814
• NM_030948.6:c.297C>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.297C>T​(p.Val99Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,613,372 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 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (5 hom.)
• Consequence: PHACTR1 NM_030948.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.180
• Publications: 3 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (REVEL=0.076).
• BP6: Variant 6-13053411-C-T is Benign according to our data. Variant chr6-13053411-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1676009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.18 with no splicing effect.
• BS2: High AC in GnomAd4 at 215 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.297C>T	p.Val99Val	synonymous	Exon 5 of 15	NP_112210.1	Q9C0D0-1
	PHACTR1	NM_001322314.4		c.300C>T	p.Val100Val	synonymous	Exon 2 of 13	NP_001309243.1	A0A6Q8PGC2
	PHACTR1	NM_001322310.2		c.297C>T	p.Val99Val	synonymous	Exon 3 of 14	NP_001309239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	ENST00000332995.12	TSL:2 MANE Select	c.297C>T	p.Val99Val	synonymous	Exon 5 of 15	ENSP00000329880.8	Q9C0D0-1
	PHACTR1	ENST00000675203.2		c.300C>T	p.Val100Val	synonymous	Exon 2 of 13	ENSP00000502172.2	A0A6Q8PGC2
	PHACTR1	ENST00000674595.1		c.297C>T	p.Val99Val	synonymous	Exon 4 of 13	ENSP00000502157.1	A0A6Q8PG87

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 215 AN: 152166 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00172

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00138 AC: 341 AN: 247898 AF XY: 0.00129

Gnomad AFR exome AF: 0.000713

Gnomad AMR exome AF: 0.00225

Gnomad ASJ exome AF: 0.00409

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.000279

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.00167

GnomAD4 exome AF: 0.00191 AC: 2793 AN: 1461088 Hom.: 5 Cov.: 30 AF XY: 0.00179 AC XY: 1299 AN XY: 726782

African (AFR) AF: 0.000956 AC: 32 AN: 33474

American (AMR) AF: 0.00199 AC: 89 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00364 AC: 95 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39662

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86114

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53352

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.00219 AC: 2435 AN: 1111620

Other (OTH) AF: 0.00189 AC: 114 AN: 60352

GnomAD4 genome AF: 0.00141 AC: 215 AN: 152284 Hom.: 1 Cov.: 33 AF XY: 0.00132 AC XY: 98 AN XY: 74482

African (AFR) AF: 0.000794 AC: 33 AN: 41542

American (AMR) AF: 0.00307 AC: 47 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00172 AC: 117 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00168 Hom.: 0

Bravo AF: 0.00161

EpiCase AF: 0.00180

EpiControl AF: 0.00214

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	-0.40
CADD	Benign	8.3
DANN	Benign	0.64
PhyloP100		-0.18
PromoterAI		0.029	Neutral
Mutation Taster		=290/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs141282814; hg19: chr6-13053643; COSMIC: COSV100275274; COSMIC: COSV100275274;