rs28934606

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_000785.4(CYP27B1):​c.1004G>C​(p.Arg335Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

CYP27B1
NM_000785.4 missense

Scores

6
11
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.46
Variant links:
Genes affected
CYP27B1 (HGNC:2606): (cytochrome P450 family 27 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The protein encoded by this gene localizes to the inner mitochondrial membrane where it hydroxylates 25-hydroxyvitamin D3 at the 1alpha position. This reaction synthesizes 1alpha,25-dihydroxyvitamin D3, the active form of vitamin D3, which binds to the vitamin D receptor and regulates calcium metabolism. Thus this enzyme regulates the level of biologically active vitamin D and plays an important role in calcium homeostasis. Mutations in this gene can result in vitamin D-dependent rickets type I. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.944
PP5
Variant 12-57764510-C-G is Pathogenic according to our data. Variant chr12-57764510-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 1660.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP27B1NM_000785.4 linkuse as main transcriptc.1004G>C p.Arg335Pro missense_variant 6/9 ENST00000228606.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP27B1ENST00000228606.9 linkuse as main transcriptc.1004G>C p.Arg335Pro missense_variant 6/91 NM_000785.4 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Vitamin D-dependent rickets, type 1A Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMar 05, 1998- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.24
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.75
D;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Uncertain
0.27
D
MetaRNN
Pathogenic
0.94
D;D
MetaSVM
Uncertain
0.17
D
MutationAssessor
Uncertain
2.9
M;.
MutationTaster
Benign
1.0
A
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-4.9
D;D
REVEL
Pathogenic
0.74
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.013
D;D
Polyphen
0.99
D;.
Vest4
0.93
MutPred
0.81
Gain of catalytic residue at E332 (P = 0.0044);.;
MVP
0.91
MPC
1.6
ClinPred
1.0
D
GERP RS
2.8
Varity_R
0.99
gMVP
0.91

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: rs28934606; hg19: chr12-58158293; API