rs755438608

chr18-62716074-TCCGCGGCCG-Tchr18-62716074-TCCGCGGCCG-TCCGCGGCCGCCGCGGCCG

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_194449.4(PHLPP1):c.403_411del(p.Ala135_Ala137del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000356 in 1,486,830 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00035 (2 hom.)
• Consequence: PHLPP1 NM_194449.4 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77

Genes affected

PHLPP1 (HGNC:20610): (PH domain and leucine rich repeat protein phosphatase 1) This gene encodes a member of the serine/threonine phosphatase family. The encoded protein promotes apoptosis by dephosphorylating and inactivating the serine/threonine kinase Akt, and functions as a tumor suppressor in multiple types of cancer. Increased expression of this gene may also play a role in obesity and type 2 diabetes by interfering with Akt-mediated insulin signaling. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_194449.4
• BS2: High AC in GnomAd at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHLPP1	NM_194449.4	c.403_411del	p.Ala135_Ala137del	inframe_deletion	1/17	ENST00000262719.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHLPP1	ENST00000262719.10	c.403_411del	p.Ala135_Ala137del	inframe_deletion	1/17	1	NM_194449.4	P1

Frequencies

GnomAD3 genomes AF: 0.000416 AC: 62 AN: 148970 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000520

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000624

Gnomad SAS AF: 0.000430

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000507

Gnomad OTH AF: 0.000486

GnomAD3 exomes AF: 0.000588 AC: 51 AN: 86784 Hom.: 1 AF XY: 0.000496 AC XY: 24 AN XY: 48420

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000225

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000682

Gnomad SAS exome AF: 0.00169

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000482

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000349 AC: 467 AN: 1337750 Hom.: 2 AF XY: 0.000386 AC XY: 254 AN XY: 658462

Gnomad4 AFR exome AF: 0.000332

Gnomad4 AMR exome AF: 0.000170

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000279

Gnomad4 SAS exome AF: 0.000823

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000343

Gnomad4 OTH exome AF: 0.000323

GnomAD4 genome AF: 0.000416 AC: 62 AN: 149080 Hom.: 0 Cov.: 31 AF XY: 0.000343 AC XY: 25 AN XY: 72848

Gnomad4 AFR AF: 0.000519

Gnomad4 AMR AF: 0.0000661

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000626

Gnomad4 SAS AF: 0.000430

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000507

Gnomad4 OTH AF: 0.000482

Alfa AF: 0.000194 Hom.: 0

Bravo AF: 0.000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Jan 30, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs755438608; hg19: chr18-60383307;