11-121303461-G-A

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The NM_006918.5(SC5D):c.86G>A(p.Arg29Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SC5D
NM_006918.5 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 9.84

Publications

6 publications found

Variant links:

Genes affected

SC5D (HGNC:10547): (sterol-C5-desaturase) This gene encodes an enzyme of cholesterol biosynthesis. The encoded protein catalyzes the conversion of lathosterol into 7-dehydrocholesterol. Mutations in this gene have been associated with lathosterolosis. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

SC5D Gene-Disease associations (from GenCC):

lathosterolosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

SC5D links:

ENSG00000299150 (HGNC:):

ENSG00000299150 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.967

PP5

Variant 11-121303461-G-A is Pathogenic according to our data. Variant chr11-121303461-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 7354.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SC5D	NM_006918.5 link	c.86G>A	p.Arg29Gln	missense_variant	Exon 2 of 5	ENST00000264027.9	NP_008849.2	O75845A0A024R3G4
SC5D	NM_001024956.3 link	c.86G>A	p.Arg29Gln	missense_variant	Exon 2 of 5		NP_001020127.1	O75845A0A024R3G4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SC5D	ENST00000264027.9 link	c.86G>A	p.Arg29Gln	missense_variant	Exon 2 of 5	1	NM_006918.5	ENSP00000264027.4		O75845

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000358

AC:

AN:

251374

AF XY:

0.0000515

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1111902

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000127

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lathosterolosis

Pathogenic:2

Jun 28, 2025

Immunogenetics and Transplant Biology Service, University Hospital "Città della Salute e della Scienza di Torino"

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 01, 2002

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.44

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.83

D;D;D;D

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

1.1

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

.;D;D;D

M_CAP

Benign

0.062

MetaRNN

Pathogenic

0.97

D;D;D;D

MetaSVM

Pathogenic

0.91

MutationAssessor

Pathogenic

4.0

H;.;.;H

PhyloP100

9.8

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.9

D;D;D;D

REVEL

Pathogenic

0.81

Sift

Uncertain

0.010

D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.85

MutPred

0.86

Gain of glycosylation at S33 (P = 0.2419);Gain of glycosylation at S33 (P = 0.2419);Gain of glycosylation at S33 (P = 0.2419);Gain of glycosylation at S33 (P = 0.2419);

MVP

0.93

MPC

0.65

ClinPred

0.90

GERP RS

6.2

Varity_R

0.51

gMVP

0.90

Mutation Taster

=3/97

disease causing (ClinVar)

(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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11-121303461-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over