20-18813891-G-A

Position:

• chr20-18813891-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178483.3(SCP2D1):​c.76G>A​(p.Gly26Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCP2D1 NM_178483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.523

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064747244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCP2D1	NM_178483.3	c.76G>A	p.Gly26Ser	missense_variant	1/1	ENST00000377428.4	NP_848578.1
SCP2D1-AS1	NR_161342.1	n.269-3776C>T		intron_variant
SCP2D1-AS1	NR_161343.1	n.245-3776C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCP2D1	ENST00000377428.4	c.76G>A	p.Gly26Ser	missense_variant	1/1	6	NM_178483.3	ENSP00000366645.2
SCP2D1-AS1	ENST00000623418.1	n.219-3776C>T		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 08, 2024

The c.76G>A (p.G26S) alteration is located in exon 1 (coding exon 1) of the SCP2D1 gene. This alteration results from a G to A substitution at nucleotide position 76, causing the glycine (G) at amino acid position 26 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.3
DANN	Benign	0.88
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.010
Sift	Benign	0.26	T
Sift4G	Benign	0.45	T
Polyphen		0.29	B
Vest4		0.097
MutPred		0.29		Gain of sheet (P = 0.0344);
MVP		0.014
MPC		0.082
ClinPred		0.29	T
GERP RS		1.1
Varity_R		0.036
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-18794535;