Variant 3-47414059-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_012235.4(SCAP):c.3635A>G(p.Asn1212Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,613,236 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 0.00019 ( 2 hom. )

Consequence

SCAP
NM_012235.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

SCAP (HGNC:30634): (SREBF chaperone) This gene encodes a protein with a sterol sensing domain (SSD) and seven WD domains. In the presence of cholesterol, this protein binds to sterol regulatory element binding proteins (SREBPs) and mediates their transport from the ER to the Golgi. The SREBPs are then proteolytically cleaved and regulate sterol biosynthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

SCAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18945006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCAP	NM_012235.4 linkuse as main transcript	c.3635A>G	p.Asn1212Ser	missense_variant	23/23	ENST00000265565.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAP	ENST00000265565.10 linkuse as main transcript	c.3635A>G	p.Asn1212Ser	missense_variant	23/23	1	NM_012235.4	P1	Q12770-1
SCAP	ENST00000648151.1 linkuse as main transcript	c.3635A>G	p.Asn1212Ser	missense_variant	24/24			P1	Q12770-1
SCAP	ENST00000320017.10 linkuse as main transcript	c.*2349A>G		3_prime_UTR_variant, NMD_transcript_variant	18/18	2
SCAP	ENST00000441517.6 linkuse as main transcript	c.*2781A>G		3_prime_UTR_variant, NMD_transcript_variant	20/20	2

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

250932

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.0000971

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000185

AC:

271

AN:

1461118

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

130

AN XY:

726826

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000238

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

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

Apr 08, 2022

The c.3635A>G (p.N1212S) alteration is located in exon 23 (coding exon 22) of the SCAP gene. This alteration results from a A to G substitution at nucleotide position 3635, causing the asparagine (N) at amino acid position 1212 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

0.054

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.65

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.29

T;T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.91

M_CAP

Benign

0.0056

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.18

N;.;N

MutationTaster

Benign

0.93

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.6

N;.;.

REVEL

Benign

0.034

Sift

Benign

0.34

T;.;.

Sift4G

Benign

0.44

T;T;.

Polyphen

0.0030

B;.;B

Vest4

0.25

MVP

0.30

MPC

0.19

ClinPred

0.030

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.089

gMVP

0.036

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

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