8-22228319-G-A

Variant names:

• chr8-22228319-G-A
• rs1218825091
• NM_014759.5:c.39C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014759.5(PHYHIP):​c.39C>T​(p.Asn13Asn) variant causes a synonymous 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: 33)
• Consequence: PHYHIP NM_014759.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.

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.39C>T	p.Asn13Asn	synonymous	Exon 2 of 5	NP_055574.3
	PHYHIP	NM_001099335.2		c.39C>T	p.Asn13Asn	synonymous	Exon 3 of 6	NP_001092805.1	Q92561
	PHYHIP	NM_001363311.2		c.39C>T	p.Asn13Asn	synonymous	Exon 3 of 7	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.39C>T	p.Asn13Asn	synonymous	Exon 2 of 5	ENSP00000415491.2	Q92561
	PHYHIP	ENST00000321613.7	TSL:1	c.39C>T	p.Asn13Asn	synonymous	Exon 3 of 6	ENSP00000320017.3	Q92561
	PHYHIP	ENST00000934692.1		c.39C>T	p.Asn13Asn	synonymous	Exon 3 of 6	ENSP00000604751.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 242196 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.9
DANN	Benign	0.70
PhyloP100		1.0

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: rs1218825091; hg19: chr8-22085832;