20-18814117-G-T

Variant names:

• chr20-18814117-G-T
• rs1568708944
• NM_178483.3:c.302G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178483.3(SCP2D1):​c.302G>T​(p.Arg101Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCP2D1 NM_178483.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCP2D1	NM_178483.3	c.302G>T	p.Arg101Met	missense_variant	Exon 1 of 1	ENST00000377428.4	NP_848578.1
SCP2D1-AS1	NR_161342.1	n.269-4002C>A		intron_variant	Intron 2 of 2
SCP2D1-AS1	NR_161343.1	n.245-4002C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCP2D1	ENST00000377428.4	c.302G>T	p.Arg101Met	missense_variant	Exon 1 of 1	6	NM_178483.3	ENSP00000366645.2
SCP2D1-AS1	ENST00000623418.1	n.219-4002C>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251420 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0092	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.16
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.025	D
Polyphen		0.98	D
Vest4		0.51
MutPred		0.38		Loss of catalytic residue at R101 (P = 0.023);
MVP		0.048
MPC		0.44
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.28
gMVP		0.20

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: rs1568708944; hg19: chr20-18794761;