NM_014759.5:c.-30+877T>C

Variant names:

• chr8-22230919-A-G
• rs12541335
• NM_014759.5:c.-30+877T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYHIP	NM_014759.5	MANE Select	c.-30+877T>C		intron	N/A	NP_055574.3
	PHYHIP	NM_001099335.2		c.-152+877T>C		intron	N/A	NP_001092805.1
	PHYHIP	NM_001363311.2		c.-152+877T>C		intron	N/A	NP_001350240.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYHIP	ENST00000454243.7	TSL:1 MANE Select	c.-30+877T>C		intron	N/A	ENSP00000415491.2
	PHYHIP	ENST00000321613.7	TSL:1	c.-152+877T>C		intron	N/A	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

African (AFR) AF: 0.195 AC: 8076 AN: 41500

American (AMR) AF: 0.354 AC: 5401 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3468

East Asian (EAS) AF: 0.0378 AC: 195 AN: 5162

South Asian (SAS) AF: 0.346 AC: 1668 AN: 4820

European-Finnish (FIN) AF: 0.343 AC: 3633 AN: 10596

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30513 AN: 67964

Other (OTH) AF: 0.354 AC: 746 AN: 2110

Alfa AF: 0.406 Hom.: 45362

Bravo AF: 0.336

Asia WGS AF: 0.206 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.42
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs12541335; hg19: chr8-22088432;