chr6-78961775-G-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_017934.7(PHIP):​c.3571C>T​(p.Gln1191*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

PHIP
NM_017934.7 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic/Likely pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 4.91
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]
IRAK1BP1 (HGNC:17368): (interleukin 1 receptor associated kinase 1 binding protein 1) Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-78961775-G-A is Pathogenic according to our data. Variant chr6-78961775-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 545398.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-78961775-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PHIPNM_017934.7 linkuse as main transcriptc.3571C>T p.Gln1191* stop_gained 31/40 ENST00000275034.5 NP_060404.4 Q8WWQ0
PHIPXM_005248729.6 linkuse as main transcriptc.3568C>T p.Gln1190* stop_gained 31/40 XP_005248786.1 A0A8V8TPV5
PHIPXM_011535918.4 linkuse as main transcriptc.3055C>T p.Gln1019* stop_gained 28/37 XP_011534220.1
IRAK1BP1XM_047418194.1 linkuse as main transcriptc.*38-17358G>A intron_variant XP_047274150.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PHIPENST00000275034.5 linkuse as main transcriptc.3571C>T p.Gln1191* stop_gained 31/401 NM_017934.7 ENSP00000275034.3 Q8WWQ0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome Pathogenic:2
Likely pathogenic, no assertion criteria providedprovider interpretationSolve-RD ConsortiumJun 01, 2022Variant confirmed as disease-causing by referring clinical team -
Pathogenic, no assertion criteria providedliterature onlyOMIMDec 02, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.65
CADD
Pathogenic
44
DANN
Uncertain
1.0
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
1.0
FATHMM_MKL
Pathogenic
0.97
D
Vest4
0.94
GERP RS
5.9
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554196907; hg19: chr6-79671492; API