rs1053839

Variant names:

• chr20-18814110-C-T
• rs1053839
• NM_178483.3:c.295C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.23 (5041 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26093 hom.)
• Consequence: SCP2D1 NM_178483.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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

ACMG classification

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCP2D1	ENST00000377428.4	c.295C>T	p.Pro99Ser	missense_variant	Exon 1 of 1	6	NM_178483.3	ENSP00000366645.2
SCP2D1-AS1	ENST00000623418.1	n.219-3995G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35363 AN: 151940 Hom.: 5033 Cov.: 32

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

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.: 33 AF XY: 0.184 AC XY: 134001 AN XY: 727034

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.: 32 AF XY: 0.232 AC XY: 17233 AN XY: 74338

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	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.6
DANN	Benign	0.68
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.00077	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.43	N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.060
Sift	Benign	0.30	T
Sift4G	Benign	0.74	T
Polyphen		0.011	B
Vest4		0.068
MPC		0.079
ClinPred		0.0039	T
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

Other links and lift over

dbSNP: rs1053839; hg19: chr20-18794754; COSMIC: COSV53857466; COSMIC: COSV53857466;