Variant rs878854420 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP5_Moderate

The NM_017934.7(PHIP):c.50T>G(p.Phe17Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,442,510 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PHIP
NM_017934.7 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.92

Variant links:

Genes affected

PHIP (HGNC:15673): (pleckstrin homology domain interacting protein) This gene encodes a protein that binds to the insulin receptor substrate 1 protein and regulates glucose transporter translocation in skeletal muscle cells. The encoded protein may also regulate growth and survival of pancreatic beta cells. Elevated copy number of this gene may be associated with melanoma severity and the encoded protein may promote melanoma metastasis in human patients. [provided by RefSeq, Oct 2016]

PHIP links:

ENSG00000286340 (HGNC:):

ENSG00000286340 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PHIP. . Gene score misZ: 5.1395 (greater than the threshold 3.09). Trascript score misZ: 4.4358 (greater than threshold 3.09). The gene has 23 curated pathogenic missense variants (we use a threshold of 10). The gene has 29 curated benign missense variants. GenCC has associacion of the gene with PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, developmental delay, intellectual disability, obesity, and dysmorphic features.

PP5

Variant 6-79077904-A-C is Pathogenic according to our data. Variant chr6-79077904-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1685399.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHIP	NM_017934.7 link	c.50T>G	p.Phe17Cys	missense_variant	2/40	ENST00000275034.5	NP_060404.4	Q8WWQ0
PHIP	XM_005248729.6 link	c.50T>G	p.Phe17Cys	missense_variant	2/40		XP_005248786.1	A0A8V8TPV5
PHIP	XM_011535919.2 link	c.50T>G	p.Phe17Cys	missense_variant	2/26		XP_011534221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHIP	ENST00000275034.5 link	c.50T>G	p.Phe17Cys	missense_variant	2/40	1	NM_017934.7	ENSP00000275034.3		Q8WWQ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442510

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.06e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Uncertain

0.74

Eigen

Benign

0.14

Eigen_PC

Benign

0.013

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.38

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.98

Vest4

0.56

MutPred

0.58

Gain of sheet (P = 0.0101);

MVP

0.82

MPC

3.0

ClinPred

1.0

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.80

gMVP

0.78

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over