chr1-154932703-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006556.4(PMVK):​c.96-288T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,224 control chromosomes in the GnomAD database, including 7,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 7363 hom., cov: 32)

Consequence

PMVK
NM_006556.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.261
Variant links:
Genes affected
PMVK (HGNC:9141): (phosphomevalonate kinase) This gene encodes a peroxisomal enzyme that is a member of the galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase (GHMP) family of ATP-dependent enzymes. The encoded protein catalyzes the conversion of mevalonate 5-phosphate to mevalonate 5-diphosphate, which is the fifth step in the mevalonate pathway of isoprenoid biosynthesis. Mutations in this gene are linked to certain types of porokeratosis including disseminated superficial porokeratosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 1-154932703-A-G is Benign according to our data. Variant chr1-154932703-A-G is described in ClinVar as [Benign]. Clinvar id is 1227224.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PMVKNM_006556.4 linkuse as main transcriptc.96-288T>C intron_variant ENST00000368467.4
PMVKNM_001323011.3 linkuse as main transcriptc.54-288T>C intron_variant
PMVKNM_001323012.3 linkuse as main transcriptc.-130-288T>C intron_variant
PMVKNM_001348696.2 linkuse as main transcriptc.-11-288T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PMVKENST00000368467.4 linkuse as main transcriptc.96-288T>C intron_variant 1 NM_006556.4 P1

Frequencies

GnomAD3 genomes
AF:
0.207
AC:
31424
AN:
152106
Hom.:
7320
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.579
Gnomad AMI
AF:
0.0154
Gnomad AMR
AF:
0.0978
Gnomad ASJ
AF:
0.0668
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.0614
Gnomad FIN
AF:
0.0553
Gnomad MID
AF:
0.158
Gnomad NFE
AF:
0.0656
Gnomad OTH
AF:
0.159
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.207
AC:
31520
AN:
152224
Hom.:
7363
Cov.:
32
AF XY:
0.201
AC XY:
14950
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.580
Gnomad4 AMR
AF:
0.0976
Gnomad4 ASJ
AF:
0.0668
Gnomad4 EAS
AF:
0.00135
Gnomad4 SAS
AF:
0.0608
Gnomad4 FIN
AF:
0.0553
Gnomad4 NFE
AF:
0.0656
Gnomad4 OTH
AF:
0.158
Alfa
AF:
0.0518
Hom.:
118
Bravo
AF:
0.225
Asia WGS
AF:
0.0930
AC:
323
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 20, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.5
DANN
Benign
0.67

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: rs7543051; hg19: chr1-154905179; API