Variant rs1053839 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:):

SCP2D1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SCP2D1	NM_178483.3 linkuse as main transcript	c.295C>T	p.Pro99Ser	missense_variant	1/1	ENST00000377428.4	NP_848578.1	Q9UJQ7
SCP2D1-AS1	NR_161342.1 linkuse as main transcript	n.269-3995G>A		intron_variant
SCP2D1-AS1	NR_161343.1 linkuse as main transcript	n.245-3995G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCP2D1	ENST00000377428.4 linkuse as main transcript	c.295C>T	p.Pro99Ser	missense_variant	1/1	6	NM_178483.3	ENSP00000366645.2		Q9UJQ7
SCP2D1-AS1	ENST00000623418.1 linkuse as main transcript	n.219-3995G>A		intron_variant		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

GnomAD3 exomes

AF:

0.185

AC:

46480

AN:

251374

Hom.:

5018

AF XY:

0.185

AC XY:

25093

AN XY:

135862

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 SAS exome

AF:

0.240

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

Gnomad4 AFR exome

AF:

0.402

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.0545

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.177

Gnomad4 OTH exome

AF:

0.193

GnomAD4 genome

AF:

0.233

AC:

35412

AN:

152058

Hom.:

5041

Cov.:

AF XY:

0.232

AC XY:

17233

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.400

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.0363

Gnomad4 SAS

AF:

0.224

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.178

Hom.:

5409

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

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

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

Varity_R

0.055

gMVP

0.067

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over