rs540128

Variant names:

• chr18-62877118-T-A
• rs540128
• NM_194449.4:c.2066+16517T>A

Your query was ambiguous. Multiple possible variants found:

• chr18-62877118-T-A
• chr18-62877118-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_194449.4(PHLPP1):​c.2066+16517T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHLPP1 NM_194449.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543
• Publications: 10 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).

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.2066+16517T>A		intron	N/A	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.2066+16517T>A		intron	N/A	ENSP00000262719.4	O60346-1
	PHLPP1	ENST00000937482.1		c.1940+16517T>A		intron	N/A	ENSP00000607541.1
	PHLPP1	ENST00000487409.1	TSL:3	n.587+16517T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.6
DANN	Benign	0.82
PhyloP100		0.54

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: rs540128; hg19: chr18-60544351;