chr10-13278279-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006214.4(PHYH):​c.*22T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,569,420 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0027 ( 21 hom. )

Consequence

PHYH
NM_006214.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0660
Variant links:
Genes affected
PHYH (HGNC:8940): (phytanoyl-CoA 2-hydroxylase) This gene is a member of the PhyH family and encodes a peroxisomal protein that is involved in the alpha-oxidation of 3-methyl branched fatty acids. Specifically, this protein converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA. Mutations in this gene have been associated with Refsum disease (RD) and deficient protein activity has been associated with Zellweger syndrome and rhizomelic chondrodysplasia punctata. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 10-13278279-A-C is Benign according to our data. Variant chr10-13278279-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 299242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00346 (527/152318) while in subpopulation NFE AF= 0.00601 (409/68042). AF 95% confidence interval is 0.00553. There are 5 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PHYHNM_006214.4 linkuse as main transcriptc.*22T>G 3_prime_UTR_variant 9/9 ENST00000263038.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PHYHENST00000263038.9 linkuse as main transcriptc.*22T>G 3_prime_UTR_variant 9/91 NM_006214.4 P1O14832-1
PHYHENST00000396913.6 linkuse as main transcriptc.*22T>G 3_prime_UTR_variant 8/85 O14832-2
PHYHENST00000396920.7 linkuse as main transcriptc.*22T>G 3_prime_UTR_variant 9/95

Frequencies

GnomAD3 genomes
AF:
0.00346
AC:
527
AN:
152200
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00490
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00678
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00601
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.00293
AC:
737
AN:
251312
Hom.:
1
AF XY:
0.00293
AC XY:
398
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.00496
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00638
Gnomad NFE exome
AF:
0.00458
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.00275
AC:
3890
AN:
1417102
Hom.:
21
Cov.:
26
AF XY:
0.00277
AC XY:
1964
AN XY:
707994
show subpopulations
Gnomad4 AFR exome
AF:
0.000491
Gnomad4 AMR exome
AF:
0.000403
Gnomad4 ASJ exome
AF:
0.00313
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00630
Gnomad4 NFE exome
AF:
0.00309
Gnomad4 OTH exome
AF:
0.00214
GnomAD4 genome
AF:
0.00346
AC:
527
AN:
152318
Hom.:
5
Cov.:
33
AF XY:
0.00364
AC XY:
271
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.000505
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00490
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00678
Gnomad4 NFE
AF:
0.00601
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.00829
Hom.:
4
Bravo
AF:
0.00204

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Phytanic acid storage disease Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.99
DANN
Benign
0.50

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.

Other links and lift over

dbSNP: rs186628076; hg19: chr10-13320279; API