Genetic Variant SCP2:p.Pro8Ser (chr1-52927418-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002979.5(SCP2):c.22C>T(p.Pro8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SCP2
NM_002979.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

Publications

0 publications found

Variant links:

Genes affected

SCP2 (HGNC:10606): (sterol carrier protein 2) This gene encodes two proteins: sterol carrier protein X (SCPx) and sterol carrier protein 2 (SCP2), as a result of transcription initiation from 2 independently regulated promoters. The transcript initiated from the proximal promoter encodes the longer SCPx protein, and the transcript initiated from the distal promoter encodes the shorter SCP2 protein, with the 2 proteins sharing a common C-terminus. Evidence suggests that the SCPx protein is a peroxisome-associated thiolase that is involved in the oxidation of branched chain fatty acids, while the SCP2 protein is thought to be an intracellular lipid transfer protein. This gene is highly expressed in organs involved in lipid metabolism, and may play a role in Zellweger syndrome, in which cells are deficient in peroxisomes and have impaired bile acid synthesis. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms.[provided by RefSeq, Aug 2010]

SCP2 links:

ECHDC2 (HGNC:23408): (enoyl-CoA hydratase domain containing 2) Predicted to enable enoyl-CoA hydratase activity. Predicted to be involved in fatty acid beta-oxidation. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ECHDC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05654514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCP2	NM_002979.5 link	c.22C>T	p.Pro8Ser	missense_variant	Exon 1 of 16	ENST00000371514.8	NP_002970.2	P22307-1A0A384NY87Q59HG9B2R761

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCP2	ENST00000371514.8 link	c.22C>T	p.Pro8Ser	missense_variant	Exon 1 of 16	1	NM_002979.5	ENSP00000360569.3		P22307-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33356

American (AMR)

AF:

0.00

AC:

AN:

42498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25780

East Asian (EAS)

AF:

0.00

AC:

AN:

39210

South Asian (SAS)

AF:

0.00

AC:

AN:

83084

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5472

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106272

Other (OTH)

AF:

0.00

AC:

AN:

59878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.14

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.17

T;.;.;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.59

T;T;T;T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.057

T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.26

N;N;N;N;.

PhyloP100

-1.5

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.030

N;N;N;N;.

REVEL

Benign

0.066

Sift

Benign

0.23

T;T;T;T;.

Sift4G

Benign

0.11

T;T;T;T;.

Polyphen

0.0

B;.;.;.;.

Vest4

0.035

MutPred

0.24

Loss of glycosylation at P8 (P = 0.0299);Loss of glycosylation at P8 (P = 0.0299);Loss of glycosylation at P8 (P = 0.0299);Loss of glycosylation at P8 (P = 0.0299);Loss of glycosylation at P8 (P = 0.0299);

MVP

0.50

MPC

0.38

ClinPred

0.059

GERP RS

-3.3

PromoterAI

-0.061

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.022

gMVP

0.53

Mutation Taster

=95/5

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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1-52927418-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over