Variant 9-128927195-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001100876.2(PHYHD1):c.191A>G(p.Gln64Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000821 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PHYHD1
NM_001100876.2 missense, splice_region

Scores

Splicing: ADA: 0.8114

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97

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:

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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
PHYHD1	NM_001100876.2 linkuse as main transcript	c.191A>G	p.Gln64Arg	missense_variant, splice_region_variant	4/13	ENST00000372592.8	NP_001094346.1	Q5SRE7-1
PHYHD1	NM_174933.4 linkuse as main transcript	c.191A>G	p.Gln64Arg	missense_variant, splice_region_variant	4/12		NP_777593.2	Q5SRE7-3A0A024R893
PHYHD1	NM_001100877.1 linkuse as main transcript	c.191A>G	p.Gln64Arg	missense_variant, splice_region_variant	2/10		NP_001094347.1	Q5SRE7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHYHD1	ENST00000372592.8 linkuse as main transcript	c.191A>G	p.Gln64Arg	missense_variant, splice_region_variant	4/13	2	NM_001100876.2	ENSP00000361673.3		Q5SRE7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251376

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135868

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 SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461658

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Nov 09, 2024

The c.191A>G (p.Q64R) alteration is located in exon 4 (coding exon 2) of the PHYHD1 gene. This alteration results from a A to G substitution at nucleotide position 191, causing the glutamine (Q) at amino acid position 64 to be replaced by an arginine (R). 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

Benign

0.30

BayesDel_addAF

Benign

0.0062

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.32

T;T;.;T;.;T;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.087

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.77

T;D;T;T;.;T;T

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.61

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.14

MutationAssessor

Benign

1.1

L;.;L;.;L;.;L

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.2

N;D;N;D;N;N;N

REVEL

Uncertain

0.54

Sift

Benign

0.033

D;D;T;D;D;T;D

Sift4G

Benign

0.065

T;D;T;D;T;T;T

Polyphen

0.60

P;.;P;.;P;.;P

Vest4

0.49

MutPred

0.69

Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);

MVP

0.24

MPC

0.20

ClinPred

0.50

GERP RS

4.3

Varity_R

0.34

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.81

dbscSNV1_RF

Benign

0.69

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