NM_030948.6:c.294C>T

Variant names:

• chr6-13053408-C-T
• rs373688362
• NM_030948.6:c.294C>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.294C>T​(p.Leu98Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,613,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: PHACTR1 NM_030948.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.313
• Publications: 0 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=0.066).
• BP6: Variant 6-13053408-C-T is Benign according to our data. Variant chr6-13053408-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3030612.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.313 with no splicing effect.
• BS2: High AC in GnomAd4 at 19 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.294C>T	p.Leu98Leu	synonymous	Exon 5 of 15	NP_112210.1	Q9C0D0-1
	PHACTR1	NM_001322314.4		c.297C>T	p.Leu99Leu	synonymous	Exon 2 of 13	NP_001309243.1	A0A6Q8PGC2
	PHACTR1	NM_001322310.2		c.294C>T	p.Leu98Leu	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.294C>T	p.Leu98Leu	synonymous	Exon 5 of 15	ENSP00000329880.8	Q9C0D0-1
	PHACTR1	ENST00000675203.2		c.297C>T	p.Leu99Leu	synonymous	Exon 2 of 13	ENSP00000502172.2	A0A6Q8PGC2
	PHACTR1	ENST00000674595.1		c.294C>T	p.Leu98Leu	synonymous	Exon 4 of 13	ENSP00000502157.1	A0A6Q8PG87

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000768 AC: 19 AN: 247506 AF XY: 0.0000670

Gnomad AFR exome AF: 0.0000650

Gnomad AMR exome AF: 0.000234

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000115 AC: 168 AN: 1460958 Hom.: 0 Cov.: 30 AF XY: 0.0000963 AC XY: 70 AN XY: 726722

African (AFR) AF: 0.000119 AC: 4 AN: 33476

American (AMR) AF: 0.000247 AC: 11 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39642

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000124 AC: 138 AN: 1111546

Other (OTH) AF: 0.000182 AC: 11 AN: 60336

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152164 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74340

African (AFR) AF: 0.000193 AC: 8 AN: 41434

American (AMR) AF: 0.000262 AC: 4 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68028

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

Alfa AF: 0.0000772 Hom.: 0

Bravo AF: 0.000155

EpiCase AF: 0.000109

EpiControl AF: 0.0000595

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	-0.33
CADD	Benign	2.4
DANN	Benign	0.87
PhyloP100		-0.31
PromoterAI		-0.053	Neutral
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs373688362; hg19: chr6-13053640; COSMIC: COSV100279378; COSMIC: COSV100279378;