20-18814147-C-T

Variant names:

• chr20-18814147-C-T
• rs376844337
• NM_178483.3:c.332C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_178483.3(SCP2D1):​c.332C>T​(p.Pro111Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000266 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: SCP2D1 NM_178483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32475454).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178483.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCP2D1	NM_178483.3	MANE Select	c.332C>T	p.Pro111Leu	missense	Exon 1 of 1	NP_848578.1	Q9UJQ7
	SCP2D1-AS1	NR_161342.1		n.269-4032G>A		intron	N/A
	SCP2D1-AS1	NR_161343.1		n.245-4032G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCP2D1	ENST00000377428.4	TSL:6 MANE Select	c.332C>T	p.Pro111Leu	missense	Exon 1 of 1	ENSP00000366645.2	Q9UJQ7
	SCP2D1-AS1	ENST00000623418.2	TSL:2	n.273-4032G>A		intron	N/A
	SCP2D1-AS1	ENST00000730019.1		n.274+11119G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000676 AC: 17 AN: 251346 AF XY: 0.0000368

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000285 AC: 417 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.000272 AC XY: 198 AN XY: 727238

African (AFR) AF: 0.000239 AC: 8 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000359 AC: 399 AN: 1112000

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74318

African (AFR) AF: 0.0000724 AC: 3 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000163 Hom.: 0

Bravo AF: 0.0000831

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.21
Sift	Uncertain	0.011	D
Sift4G	Benign	0.31	T
Polyphen		0.96	D
Vest4		0.48
MVP		0.11
MPC		0.42
ClinPred		0.35	T
GERP RS		6.1
PromoterAI		-0.0023	Neutral
Varity_R		0.28
gMVP		0.23
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs376844337; hg19: chr20-18794791; COSMIC: COSV53857495; COSMIC: COSV53857495;