6-13286236-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_030948.6(PHACTR1):c.1727+24dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,370,204 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.012 (1 hom.)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.588

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.

• BP6: Variant 6-13286236-G-GT is Benign according to our data. Variant chr6-13286236-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 3024709.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0122 (14877/1221312) while in subpopulation AMR AF= 0.0168 (432/25712). AF 95% confidence interval is 0.0155. There are 1 homozygotes in gnomad4_exome. There are 7465 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd at 279 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.1727+24dup		intron_variant		ENST00000332995.12
TBC1D7-LOC100130357	NR_134872.2	n.713-4684_713-4683insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.1727+24dup		intron_variant		2	NM_030948.6	P3
	ENST00000606150.5	n.319-4684_319-4683insA		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 279 AN: 148780 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00437

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.00570

Gnomad SAS AF: 0.00171

Gnomad FIN AF: 0.000300

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00167

Gnomad OTH AF: 0.00393

GnomAD4 exome AF: 0.0122 AC: 14877 AN: 1221312 Hom.: 1 Cov.: 29 AF XY: 0.0124 AC XY: 7465 AN XY: 602202

Gnomad4 AFR exome AF: 0.0114

Gnomad4 AMR exome AF: 0.0168

Gnomad4 ASJ exome AF: 0.0129

Gnomad4 EAS exome AF: 0.0152

Gnomad4 SAS exome AF: 0.0151

Gnomad4 FIN exome AF: 0.00691

Gnomad4 NFE exome AF: 0.0120

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.00187 AC: 278 AN: 148892 Hom.: 1 Cov.: 32 AF XY: 0.00180 AC XY: 131 AN XY: 72616

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00437

Gnomad4 ASJ AF: 0.00117

Gnomad4 EAS AF: 0.00552

Gnomad4 SAS AF: 0.00171

Gnomad4 FIN AF: 0.000300

Gnomad4 NFE AF: 0.00167

Gnomad4 OTH AF: 0.00389

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

PHACTR1: BS1 -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs750206884; hg19: chr6-13286468;