dbSNP rs1053839: SCP2D1:p.Pro99Ser (chr20-18814110-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178483.3(SCP2D1):c.295C>T(p.Pro99Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,613,460 control chromosomes in the GnomAD database, including 31,134 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 5041 hom., cov: 32)

Exomes 𝑓: 0.18 ( 26093 hom. )

Consequence

SCP2D1
NM_178483.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0700

Publications

19 publications found

Variant links:

Genes affected

SCP2D1 (HGNC:16211): (SCP2 sterol binding domain containing 1) Predicted to enable sterol binding activity. Predicted to be involved in phospholipid transport; positive regulation of intracellular cholesterol transport; and steroid biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

SCP2D1 links:

SCP2D1-AS1 (HGNC:16210): (SCP2D1 antisense RNA 1)

SCP2D1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.657707E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCP2D1	NM_178483.3 link	c.295C>T	p.Pro99Ser	missense_variant	Exon 1 of 1	ENST00000377428.4	NP_848578.1	Q9UJQ7
SCP2D1-AS1	NR_161342.1 link	n.269-3995G>A		intron_variant	Intron 2 of 2
SCP2D1-AS1	NR_161343.1 link	n.245-3995G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCP2D1	ENST00000377428.4 link	c.295C>T	p.Pro99Ser	missense_variant	Exon 1 of 1	6	NM_178483.3	ENSP00000366645.2	Q9UJQ7
SCP2D1-AS1	ENST00000623418.2 link	n.273-3995G>A		intron_variant	Intron 2 of 2	2
SCP2D1-AS1	ENST00000730019.1 link	n.274+11156G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35363

AN:

151940

Hom.:

5033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.0366

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.212

GnomAD2 exomes

AF:

0.185

AC:

46480

AN:

251374

AF XY:

0.185

show subpopulations

Gnomad AFR exome

AF:

0.403

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.0353

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.183

AC:

267429

AN:

1461402

Hom.:

26093

Cov.:

AF XY:

0.184

AC XY:

134001

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.402

AC:

13470

AN:

33466

American (AMR)

AF:

0.168

AC:

7521

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

3998

AN:

26134

East Asian (EAS)

AF:

0.0545

AC:

2162

AN:

39700

South Asian (SAS)

AF:

0.235

AC:

20309

AN:

86256

European-Finnish (FIN)

AF:

0.192

AC:

10270

AN:

53416

Middle Eastern (MID)

AF:

0.192

AC:

1109

AN:

5762

European-Non Finnish (NFE)

AF:

0.177

AC:

196933

AN:

1111568

Other (OTH)

AF:

0.193

AC:

11657

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

11693

23385

35078

46770

58463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7120

14240

21360

28480

35600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.233

AC:

35412

AN:

152058

Hom.:

5041

Cov.:

AF XY:

0.232

AC XY:

17233

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.400

AC:

16563

AN:

41428

American (AMR)

AF:

0.195

AC:

2986

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

565

AN:

3468

East Asian (EAS)

AF:

0.0363

AC:

188

AN:

5182

South Asian (SAS)

AF:

0.224

AC:

1079

AN:

4816

European-Finnish (FIN)

AF:

0.190

AC:

2013

AN:

10576

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11496

AN:

67988

Other (OTH)

AF:

0.210

AC:

442

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1282

2564

3846

5128

6410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.187

Hom.:

12109

Bravo

AF:

0.239

TwinsUK

AF:

0.168

AC:

622

ALSPAC

AF:

0.174

AC:

672

ESP6500AA

AF:

0.378

AC:

1664

ESP6500EA

AF:

0.174

AC:

1500

ExAC

AF:

0.188

AC:

22867

Asia WGS

AF:

0.164

AC:

571

AN:

3478

EpiCase

AF:

0.174

EpiControl

AF:

0.173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.6

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.023

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.38

MetaRNN

Benign

0.00077

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.43

PhyloP100

0.070

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.060

Sift

Benign

0.30

Sift4G

Benign

0.74

Polyphen

0.011

Vest4

0.068

MPC

0.079

ClinPred

0.0039

GERP RS

-3.5

PromoterAI

0.0016

Neutral

(source)

Varity_R

0.055

gMVP

0.067

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over