rs554372811

Variant names:

• chr6-13281154-ACT-A
• rs554372811
• NM_030948.6:c.1510-2265_1510-2264delCT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_030948.6(PHACTR1):​c.1510-2265_1510-2264delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,279,328 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000059 (1 hom.)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.104
• 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]

TBC1D7-LOC100130357 (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]

TBC1D7 Gene-Disease associations (from GenCC):

• macrocephaly/megalencephaly syndrome, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 6-13281154-ACT-A is Benign according to our data. Variant chr6-13281154-ACT-A is described in ClinVar as Benign. ClinVar VariationId is 1695149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 74 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.1510-2265_1510-2264delCT		intron	N/A	NP_112210.1	Q9C0D0-1
	PHACTR1	NM_001322314.4		c.1720-2265_1720-2264delCT		intron	N/A	NP_001309243.1	A0A6Q8PGC2
	PHACTR1	NM_001322310.2		c.1717-2265_1717-2264delCT		intron	N/A	NP_001309239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	ENST00000332995.12	TSL:2 MANE Select	c.1510-2278_1510-2277delCT		intron	N/A	ENSP00000329880.8	Q9C0D0-1
	PHACTR1	ENST00000675203.2		c.1720-2278_1720-2277delCT		intron	N/A	ENSP00000502172.2	A0A6Q8PGC2
	PHACTR1	ENST00000674595.1		c.1510-2278_1510-2277delCT		intron	N/A	ENSP00000502157.1	A0A6Q8PG87

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152126 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000938 AC: 12 AN: 127912 AF XY: 0.0000866

Gnomad AFR exome AF: 0.00126

Gnomad AMR exome AF: 0.000170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000594 AC: 67 AN: 1127084 Hom.: 1 AF XY: 0.0000453 AC XY: 25 AN XY: 551792

African (AFR) AF: 0.00186 AC: 45 AN: 24172

American (AMR) AF: 0.000146 AC: 4 AN: 27430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15164

East Asian (EAS) AF: 0.00 AC: 0 AN: 12692

South Asian (SAS) AF: 0.00 AC: 0 AN: 74810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12734

Middle Eastern (MID) AF: 0.000231 AC: 1 AN: 4334

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 914664

Other (OTH) AF: 0.000414 AC: 17 AN: 41084

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152244 Hom.: 0 Cov.: 33 AF XY: 0.000551 AC XY: 41 AN XY: 74442

African (AFR) AF: 0.00164 AC: 68 AN: 41534

American (AMR) AF: 0.000327 AC: 5 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000304 Hom.: 0

Bravo AF: 0.000533

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.10

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

Other links and lift over

dbSNP: rs554372811; hg19: chr6-13281386;