chr11-121303550-G-A

Variant names:

Variant summary

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

The NM_006918.5(SC5D):c.175G>A(p.Asp59Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,316 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SC5D
NM_006918.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 9.88

Publications

0 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: 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
SC5D	NM_006918.5 link	c.175G>A	p.Asp59Asn	missense_variant	Exon 2 of 5	ENST00000264027.9	NP_008849.2	O75845A0A024R3G4
SC5D	NM_001024956.3 link	c.175G>A	p.Asp59Asn	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.175G>A	p.Asp59Asn	missense_variant	Exon 2 of 5	1	NM_006918.5	ENSP00000264027.4		O75845

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251152

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461414

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727046

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33466

American (AMR)

AF:

0.0000224

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111652

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151902

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41322

American (AMR)

AF:

0.0000655

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67988

Other (OTH)

AF:

0.000480

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000261

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Sep 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.175G>A (p.D59N) alteration is located in exon 2 (coding exon 1) of the SC5D gene. This alteration results from a G to A substitution at nucleotide position 175, causing the aspartic acid (D) at amino acid position 59 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Sep 24, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces aspartic acid with asparagine at codon 59 of the SC5D protein (p.Asp59Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs148156529, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with SC5D-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.72

D;T;T;D

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.94

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

.;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.73

D;D;D;D

MetaSVM

Uncertain

0.59

MutationAssessor

Uncertain

2.7

M;.;.;M

PhyloP100

9.9

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-4.3

D;D;D;D

REVEL

Uncertain

0.53

Sift

Benign

0.031

D;D;T;D

Sift4G

Benign

0.083

T;T;T;T

Polyphen

0.93

P;D;D;P

Vest4

0.84

MVP

0.95

MPC

0.52

ClinPred

0.92

GERP RS

6.2

Varity_R

0.41

gMVP

0.89

Mutation Taster

=33/67

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr11-121303550-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over