Genetic Variant SCP2D1:p.Thr85Thr (chr20-18814070-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_178483.3(SCP2D1):c.255C>T(p.Thr85Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,613,420 control chromosomes in the GnomAD database, including 28,873 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4640 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24233 hom. )

Consequence

SCP2D1
NM_178483.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.435

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=0.435 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCP2D1	NM_178483.3 link	c.255C>T	p.Thr85Thr	synonymous_variant	Exon 1 of 1	ENST00000377428.4	NP_848578.1	Q9UJQ7
SCP2D1-AS1	NR_161342.1 link	n.269-3955G>A		intron_variant	Intron 2 of 2
SCP2D1-AS1	NR_161343.1 link	n.245-3955G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCP2D1	ENST00000377428.4 link	c.255C>T	p.Thr85Thr	synonymous_variant	Exon 1 of 1	6	NM_178483.3	ENSP00000366645.2		Q9UJQ7
SCP2D1-AS1	ENST00000623418.1 link	n.219-3955G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33905

AN:

151988

Hom.:

4633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.0293

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.201

GnomAD3 exomes

AF:

0.175

AC:

43979

AN:

251382

Hom.:

4565

AF XY:

0.176

AC XY:

23907

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.0272

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.176

AC:

257151

AN:

1461314

Hom.:

24233

Cov.:

AF XY:

0.177

AC XY:

128936

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.386

Gnomad4 AMR exome

AF:

0.134

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.0428

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.223

AC:

33951

AN:

152106

Hom.:

4640

Cov.:

AF XY:

0.222

AC XY:

16525

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.0290

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.199

Alfa

AF:

0.172

Hom.:

3154

Bravo

AF:

0.227

Asia WGS

AF:

0.151

AC:

525

AN:

3478

EpiCase

AF:

0.169

EpiControl

AF:

0.168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.7

DANN

Benign

0.64

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