6-78940496-T-TTA

Variant names:

• chr6-78940496-T-TTA
• rs55984056
• NM_017934.7:c.*195_*196dupTA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_017934.7(PHIP):​c.*195_*196dupTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHIP NM_017934.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017934.7. 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
	PHIP	NM_017934.7	MANE Select	c.*195_*196dupTA		3_prime_UTR	Exon 40 of 40	NP_060404.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHIP	ENST00000275034.5	TSL:1 MANE Select	c.*195_*196dupTA		3_prime_UTR	Exon 40 of 40	ENSP00000275034.3	Q8WWQ0
	IRAK1BP1	ENST00000606868.5	TSL:1	n.*68-4894_*68-4893dupAT		intron	N/A	ENSP00000475570.1	U3KQ57
	PHIP	ENST00000913657.1		c.*195_*196dupTA		3_prime_UTR	Exon 40 of 40	ENSP00000583716.1

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 6 AN: 130100 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000855

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000245

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000312

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 718 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 386

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 18

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26

East Asian (EAS) AF: 0.00 AC: 0 AN: 46

South Asian (SAS) AF: 0.00 AC: 0 AN: 12

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 180

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 396

Other (OTH) AF: 0.00 AC: 0 AN: 32

GnomAD4 genome AF: 0.0000461 AC: 6 AN: 130100 Hom.: 0 Cov.: 0 AF XY: 0.0000328 AC XY: 2 AN XY: 61038

African (AFR) AF: 0.0000855 AC: 3 AN: 35080

American (AMR) AF: 0.00 AC: 0 AN: 11610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3310

East Asian (EAS) AF: 0.00 AC: 0 AN: 4444

South Asian (SAS) AF: 0.000245 AC: 1 AN: 4080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.0000312 AC: 2 AN: 64126

Other (OTH) AF: 0.00 AC: 0 AN: 1754

Alfa AF: 0.00 Hom.: 569

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.56

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs55984056; hg19: chr6-79650213;