NM_178483.3:c.83T>A

Variant names:

• chr20-18813898-T-A
• NM_178483.3:c.83T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178483.3(SCP2D1):​c.83T>A​(p.Val28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V28I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCP2D1 NM_178483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.528
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06559017).

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.83T>A	p.Val28Asp	missense	Exon 1 of 1	NP_848578.1	Q9UJQ7
	SCP2D1-AS1	NR_161342.1		n.269-3783A>T		intron	N/A
	SCP2D1-AS1	NR_161343.1		n.245-3783A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCP2D1	ENST00000377428.4	TSL:6 MANE Select	c.83T>A	p.Val28Asp	missense	Exon 1 of 1	ENSP00000366645.2	Q9UJQ7
	SCP2D1-AS1	ENST00000623418.2	TSL:2	n.273-3783A>T		intron	N/A
	SCP2D1-AS1	ENST00000730019.1		n.274+11368A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.070
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.9
DANN	Benign	0.69
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.53
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.019
Sift	Benign	0.18	T
Sift4G	Benign	0.075	T
Polyphen		0.11	B
Vest4		0.20
MutPred		0.29		Gain of disorder (P = 0.0198)
MVP		0.040
MPC		0.13
ClinPred		0.21	T
GERP RS		2.7
PromoterAI		0.0032	Neutral
Varity_R		0.088
gMVP		0.44
Mutation Taster		=99/1	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

hg19: chr20-18794542;