Genetic Variant NM_001100876.2:c.103A>T (chr9-128927107-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001100876.2(PHYHD1):c.103A>T(p.Arg35Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

PHYHD1
NM_001100876.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.981

Publications

2 publications found

Variant links:

Genes affected

PHYHD1 (HGNC:23396): (phytanoyl-CoA dioxygenase domain containing 1) Enables 2-oxoglutarate-dependent dioxygenase activity. [provided by Alliance of Genome Resources, Apr 2022]

PHYHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100876.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHYHD1	NM_001100876.2	MANE Select	c.103A>T	p.Arg35Trp	missense	Exon 4 of 13	NP_001094346.1	Q5SRE7-1
PHYHD1	NM_174933.4		c.103A>T	p.Arg35Trp	missense	Exon 4 of 12	NP_777593.2	Q5SRE7-3
PHYHD1	NM_001100877.1		c.103A>T	p.Arg35Trp	missense	Exon 2 of 10	NP_001094347.1	Q5SRE7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHYHD1	ENST00000372592.8	TSL:2 MANE Select	c.103A>T	p.Arg35Trp	missense	Exon 4 of 13	ENSP00000361673.3	Q5SRE7-1
PHYHD1	ENST00000308941.9	TSL:1	c.103A>T	p.Arg35Trp	missense	Exon 4 of 12	ENSP00000309515.5	Q5SRE7-3
PHYHD1	ENST00000421063.6	TSL:1	c.103A>T	p.Arg35Trp	missense	Exon 2 of 10	ENSP00000409928.2	Q5SRE7-2

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000795

AC:

AN:

251490

AF XY:

0.0000515

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000828

AC:

121

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33480

American (AMR)

AF:

0.000179

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000665

AC:

AN:

1111996

Other (OTH)

AF:

0.000265

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.000322

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.000626

AC:

AN:

41528

American (AMR)

AF:

0.00118

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.000427

Hom.:

Bravo

AF:

0.000540

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Uncertain

0.37

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.45

MetaSVM

Uncertain

0.29

MutationAssessor

Pathogenic

3.1

PhyloP100

0.98

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.59

Sift

Uncertain

0.015

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.50

MVP

0.67

MPC

0.61

ClinPred

0.84

GERP RS

3.2

Varity_R

0.73

gMVP

0.71

Mutation Taster

=73/27

polymorphism

(source)

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

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