rs755438608

Variant names:

• chr18-62716074-TCCGCGGCCG-T
• rs755438608
• NM_194449.4:c.403_411delGCGGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chr18-62716074-TCCGCGGCCG-T
• chr18-62716074-TCCGCGGCCG-TCCGCGGCCGCCGCGGCCG

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_194449.4(PHLPP1):​c.403_411delGCGGCCGCC​(p.Ala135_Ala137del) variant causes a conservative 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 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_194449.4
• BS2: High AC in GnomAd4 at 62 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194449.4. 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
	PHLPP1	NM_194449.4	MANE Select	c.403_411delGCGGCCGCC	p.Ala135_Ala137del	conservative_inframe_deletion	Exon 1 of 17	NP_919431.2	O60346-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHLPP1	ENST00000262719.10	TSL:1 MANE Select	c.403_411delGCGGCCGCC	p.Ala135_Ala137del	conservative_inframe_deletion	Exon 1 of 17	ENSP00000262719.4	O60346-1
	PHLPP1	ENST00000937482.1		c.403_411delGCGGCCGCC	p.Ala135_Ala137del	conservative_inframe_deletion	Exon 1 of 16	ENSP00000607541.1

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

GnomAD2 exomes AF: 0.000588 AC: 51 AN: 86784 AF XY: 0.000496

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 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

African (AFR) AF: 0.000332 AC: 9 AN: 27092

American (AMR) AF: 0.000170 AC: 5 AN: 29356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22580

East Asian (EAS) AF: 0.000279 AC: 9 AN: 32306

South Asian (SAS) AF: 0.000823 AC: 60 AN: 72944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32492

Middle Eastern (MID) AF: 0.000465 AC: 2 AN: 4304

European-Non Finnish (NFE) AF: 0.000343 AC: 364 AN: 1060938

Other (OTH) AF: 0.000323 AC: 18 AN: 55738

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

African (AFR) AF: 0.000519 AC: 21 AN: 40500

American (AMR) AF: 0.0000661 AC: 1 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.000626 AC: 3 AN: 4794

South Asian (SAS) AF: 0.000430 AC: 2 AN: 4650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.000507 AC: 34 AN: 67020

Other (OTH) AF: 0.000482 AC: 1 AN: 2076

Alfa AF: 0.000194 Hom.: 0

Bravo AF: 0.000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

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		1.8
Mutation Taster		=263/37	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs755438608; hg19: chr18-60383307;