6-13053389-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2 BP4

The NM_030948.6(PHACTR1):c.275C>T(p.Ala92Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000823 in 1,457,528 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: PHACTR1 NM_030948.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PP2: Missense variant where missense usually causes diseases, PHACTR1
• BP4: Computational evidence support a benign effect (MetaRNN=0.39720157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.275C>T	p.Ala92Val	missense_variant	5/15	ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.275C>T	p.Ala92Val	missense_variant	5/15	2	NM_030948.6	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000823 AC: 12 AN: 1457528 Hom.: 0 Cov.: 30 AF XY: 0.00000966 AC XY: 7 AN XY: 724762

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000631

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 70 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Feb 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.028	T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.40	N;N
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.18
Sift	Benign	0.16	T;T
Sift4G	Benign	0.46	T;T
Polyphen		0.99	D;D
Vest4		0.40
MutPred		0.26		Loss of disorder (P = 0.07);Loss of disorder (P = 0.07);
MVP		0.40
ClinPred		0.66	D
GERP RS		5.8
Varity_R		0.090
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs767982489; hg19: chr6-13053621; COSMIC: COSV60674729; COSMIC: COSV60674729;