8-22230919-A-G

Position:

• chr8-22230919-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014759.5(PHYHIP):​c.-30+877T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,100 control chromosomes in the GnomAD database, including 10,135 homozygotes. 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: 𝑓 0.34 (10135 hom., cov: 32)
• Consequence: PHYHIP NM_014759.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHYHIP	NM_014759.5	c.-30+877T>C		intron_variant		ENST00000454243.7	NP_055574.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHYHIP	ENST00000454243.7	c.-30+877T>C		intron_variant		1	NM_014759.5	ENSP00000415491.2
PHYHIP	ENST00000321613.7	c.-152+877T>C		intron_variant		1		ENSP00000320017.3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52290 AN: 151982 Hom.: 10137 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.0373

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.344 AC: 52305 AN: 152100 Hom.: 10135 Cov.: 32 AF XY: 0.337 AC XY: 25075 AN XY: 74346

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.0378

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.354

Alfa AF: 0.420 Hom.: 19406

Bravo AF: 0.336

Asia WGS AF: 0.206 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs12541335; hg19: chr8-22088432;