6-13287083-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_030948.6(PHACTR1):c.*5C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000621 in 1,605,068 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (7 hom.)
• Consequence: PHACTR1 NM_030948.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00500

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]

(HGNC:):

TBC1D7 (HGNC:21066): (TBC1 domain family member 7) This gene encodes a member of the TBC-domain containing protein family. The encoded protein functions as a subunit of the tuberous sclerosis TSC1-TSC2 complex which plays a role in the regulation of cellular growth and differentiation. Mutations in this gene have been associated with autosomal recessive megalencephaly. Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between this locus and downstream LOC100130357. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 6-13287083-C-T is Benign according to our data. Variant chr6-13287083-C-T is described in ClinVar as [Benign]. Clinvar id is 3038786.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 496 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.*5C>T		3_prime_UTR_variant	15/15	ENST00000332995.12
TBC1D7-LOC100130357	NR_134872.2	n.713-5530G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.*5C>T		3_prime_UTR_variant	15/15	2	NM_030948.6	P3
	ENST00000606150.5	n.319-5530G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00326 AC: 496 AN: 152180 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000782 AC: 183 AN: 234082 Hom.: 4 AF XY: 0.000570 AC XY: 72 AN XY: 126422

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.000584

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000568

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.000345 AC: 501 AN: 1452770 Hom.: 7 Cov.: 30 AF XY: 0.000269 AC XY: 194 AN XY: 721714

Gnomad4 AFR exome AF: 0.0105

Gnomad4 AMR exome AF: 0.000554

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000237

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000722

Gnomad4 OTH exome AF: 0.000698

GnomAD4 genome AF: 0.00325 AC: 495 AN: 152298 Hom.: 3 Cov.: 33 AF XY: 0.00295 AC XY: 220 AN XY: 74474

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00131 Hom.: 1

Bravo AF: 0.00401

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PHACTR1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	11
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs114265092; hg19: chr6-13287315;