dbSNP rs373466702: CYP27C1:p.Gly313Asp (chr2-127199485-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001367502.1(CYP27C1):c.938G>A(p.Gly313Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CYP27C1
NM_001367502.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

Publications

0 publications found

Variant links:

Genes affected

CYP27C1 (HGNC:33480): (cytochrome P450 family 27 subfamily C 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. [provided by RefSeq, Jul 2008]

CYP27C1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP27C1	NM_001367502.1 link	c.938G>A	p.Gly313Asp	missense_variant	Exon 5 of 9	ENST00000664447.2	NP_001354431.1
CYP27C1	NM_001001665.4 link	c.443G>A	p.Gly148Asp	missense_variant	Exon 4 of 8		NP_001001665.3	Q4G0S4-1A1P3N0
CYP27C1	NM_001367501.1 link	c.443G>A	p.Gly148Asp	missense_variant	Exon 4 of 8		NP_001354430.1
CYP27C1	XM_024452838.2 link	c.575G>A	p.Gly192Asp	missense_variant	Exon 5 of 9		XP_024308606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP27C1	ENST00000664447.2 link	c.938G>A	p.Gly313Asp	missense_variant	Exon 5 of 9		NM_001367502.1	ENSP00000499243.1	A0A7N4I3A3
CYP27C1	ENST00000335247.11 link	c.443G>A	p.Gly148Asp	missense_variant	Exon 4 of 8	1		ENSP00000334128.7	Q4G0S4-1
CYP27C1	ENST00000409327.2 link	c.443G>A	p.Gly148Asp	missense_variant	Exon 4 of 8	2		ENSP00000387198.1	Q4G0S4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251402

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

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

Jun 11, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.443G>A (p.G148D) alteration is located in exon 4 (coding exon 3) of the CYP27C1 gene. This alteration results from a G to A substitution at nucleotide position 443, causing the glycine (G) at amino acid position 148 to be replaced by an aspartic acid (D). 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

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.55

.;T

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

L;L

PhyloP100

4.7

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.12

Sift

Benign

0.089

T;T

Sift4G

Uncertain

0.052

T;T

Polyphen

0.43

B;B

Vest4

0.67

MVP

0.30

MPC

1.0

ClinPred

0.87

GERP RS

4.1

Varity_R

0.42

gMVP

0.77

Mutation Taster

=84/16

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over