Variant 20-18814162-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178483.3(SCP2D1):c.347T>C(p.Met116Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SCP2D1
NM_178483.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

Variant links:

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 links:

SCP2D1-AS1 (HGNC:):

SCP2D1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15870696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCP2D1	NM_178483.3 linkuse as main transcript	c.347T>C	p.Met116Thr	missense_variant	1/1	ENST00000377428.4	NP_848578.1	Q9UJQ7
SCP2D1-AS1	NR_161342.1 linkuse as main transcript	n.269-4047A>G		intron_variant
SCP2D1-AS1	NR_161343.1 linkuse as main transcript	n.245-4047A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCP2D1	ENST00000377428.4 linkuse as main transcript	c.347T>C	p.Met116Thr	missense_variant	1/1	6	NM_178483.3	ENSP00000366645.2		Q9UJQ7
SCP2D1-AS1	ENST00000623418.1 linkuse as main transcript	n.219-4047A>G		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

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

AF:

0.0000131

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.347T>C (p.M116T) alteration is located in exon 1 (coding exon 1) of the SCP2D1 gene. This alteration results from a T to C substitution at nucleotide position 347, causing the methionine (M) at amino acid position 116 to be replaced by a threonine (T). 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

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0084

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.032

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.44

M_CAP

Benign

0.0094

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.093

Sift

Benign

0.083

Sift4G

Benign

0.10

Polyphen

0.31

Vest4

0.35

MutPred

0.54

Loss of stability (P = 0.0481);

MVP

0.014

MPC

0.093

ClinPred

0.75

GERP RS

3.8

Varity_R

0.25

gMVP

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over