Genetic Variant PHYHIP:p.Gln161Arg (chr8-22221864-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014759.5(PHYHIP):c.482A>G(p.Gln161Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000583 in 1,542,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

PHYHIP
NM_014759.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10099968).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHYHIP	NM_014759.5	MANE Select	c.482A>G	p.Gln161Arg	missense	Exon 5 of 5	NP_055574.3
PHYHIP	NM_001099335.2		c.482A>G	p.Gln161Arg	missense	Exon 6 of 6	NP_001092805.1	Q92561
PHYHIP	NM_001363311.2		c.482A>G	p.Gln161Arg	missense	Exon 6 of 7	NP_001350240.1	Q92561

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHYHIP	ENST00000454243.7	TSL:1 MANE Select	c.482A>G	p.Gln161Arg	missense	Exon 5 of 5	ENSP00000415491.2	Q92561
PHYHIP	ENST00000321613.7	TSL:1	c.482A>G	p.Gln161Arg	missense	Exon 6 of 6	ENSP00000320017.3	Q92561
PHYHIP	ENST00000934692.1		c.482A>G	p.Gln161Arg	missense	Exon 6 of 6	ENSP00000604751.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152050

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000132

AC:

AN:

151668

AF XY:

0.0000125

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000326

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000503

AC:

AN:

1390946

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32000

American (AMR)

AF:

0.00

AC:

AN:

35776

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24030

East Asian (EAS)

AF:

0.00

AC:

AN:

36590

South Asian (SAS)

AF:

0.00

AC:

AN:

77788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.00000652

AC:

AN:

1073988

Other (OTH)

AF:

0.00

AC:

AN:

57624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000863

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.10

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.75

M_CAP

Benign

0.0040

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

PhyloP100

2.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.4

REVEL

Benign

0.045

Sift

Benign

0.45

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.068

MutPred

0.20

Loss of methylation at K165 (P = 0.0601)

MVP

0.11

MPC

1.3

ClinPred

0.045

GERP RS

3.9

Varity_R

0.15

gMVP

0.62

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over