8-22221875-CCC-TCG

Variant names:

• chr8-22221875-CCC-TCG
• NM_014759.5:c.469_471delGGGinsCGA
• PHYHIP p.Gly157Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014759.5(PHYHIP):​c.469_471delGGGinsCGA​(p.Gly157Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PHYHIP NM_014759.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.68
• Publications: 0 publications found

Genes affected

PHYHIP (HGNC:16865): (phytanoyl-CoA 2-hydroxylase interacting protein) Enables protein tyrosine kinase binding activity. Involved in protein localization. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014759.5. 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
	PHYHIP	NM_014759.5	MANE Select	c.469_471delGGGinsCGA	p.Gly157Arg	missense	N/A	NP_055574.3
	PHYHIP	NM_001099335.2		c.469_471delGGGinsCGA	p.Gly157Arg	missense	N/A	NP_001092805.1	Q92561
	PHYHIP	NM_001363311.2		c.469_471delGGGinsCGA	p.Gly157Arg	missense	N/A	NP_001350240.1	Q92561

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYHIP	ENST00000454243.7	TSL:1 MANE Select	c.469_471delGGGinsCGA	p.Gly157Arg	missense	N/A	ENSP00000415491.2	Q92561
	PHYHIP	ENST00000321613.7	TSL:1	c.469_471delGGGinsCGA	p.Gly157Arg	missense	N/A	ENSP00000320017.3	Q92561
	PHYHIP	ENST00000934692.1		c.469_471delGGGinsCGA	p.Gly157Arg	missense	N/A	ENSP00000604751.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7

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

hg19: chr8-22079388;