Variant 8-22221627-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014759.5(PHYHIP):c.719C>T(p.Ala240Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,332 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PHYHIP
NM_014759.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Variant links:

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]

PHYHIP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHYHIP	NM_014759.5 linkuse as main transcript	c.719C>T	p.Ala240Val	missense_variant	5/5	ENST00000454243.7	NP_055574.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PHYHIP	ENST00000454243.7 linkuse as main transcript	c.719C>T	p.Ala240Val	missense_variant	5/5	1	NM_014759.5	ENSP00000415491	P1
PHYHIP	ENST00000321613.7 linkuse as main transcript	c.719C>T	p.Ala240Val	missense_variant	6/6	1		ENSP00000320017	P1
PHYHIP	ENST00000523252.1 linkuse as main transcript	c.575C>T	p.Ala192Val	missense_variant	4/4	5		ENSP00000430870

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000816

AC:

AN:

244974

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133388

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461170

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.719C>T (p.A240V) alteration is located in exon 6 (coding exon 4) of the PHYHIP gene. This alteration results from a C to T substitution at nucleotide position 719, causing the alanine (A) at amino acid position 240 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

T;T;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.97

.;D;D

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.65

D;D;D

MetaSVM

Benign

-0.73

MutationAssessor

Benign

2.0

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.5

N;N;N

REVEL

Uncertain

0.41

Sift

Uncertain

0.021

D;D;D

Sift4G

Uncertain

0.012

D;D;T

Polyphen

1.0

D;D;.

Vest4

0.74

MutPred

0.55

Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);.;

MVP

0.52

MPC

2.3

ClinPred

0.81

GERP RS

5.5

Varity_R

0.23

gMVP

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over