rs12487736

Variant names:

• chr3-47418189-C-A
• rs12487736
• NM_012235.4:c.2392G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-47418189-C-A
• chr3-47418189-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012235.4(SCAP):​c.2392G>T​(p.Val798Phe) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCAP NM_012235.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 58 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38319468).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012235.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAP	NM_012235.4	MANE Select	c.2392G>T	p.Val798Phe	missense	Exon 16 of 23	NP_036367.2
	SCAP	NM_001320044.2		c.1627G>T	p.Val543Phe	missense	Exon 13 of 20	NP_001306973.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAP	ENST00000265565.10	TSL:1 MANE Select	c.2392G>T	p.Val798Phe	missense	Exon 16 of 23	ENSP00000265565.5
	SCAP	ENST00000648151.1		c.2392G>T	p.Val798Phe	missense	Exon 17 of 24	ENSP00000497087.1
	SCAP	ENST00000320017.10	TSL:2	n.*1109G>T		non_coding_transcript_exon	Exon 11 of 18	ENSP00000324296.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1422896 Hom.: 0 Cov.: 66 AF XY: 0.00 AC XY: 0 AN XY: 704392

African (AFR) AF: 0.00 AC: 0 AN: 32564

American (AMR) AF: 0.00 AC: 0 AN: 39354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25374

East Asian (EAS) AF: 0.00 AC: 0 AN: 37574

South Asian (SAS) AF: 0.00 AC: 0 AN: 81428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092966

Other (OTH) AF: 0.00 AC: 0 AN: 58924

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.92	T
PhyloP100		3.2
Sift4G	Pathogenic	0.0	D
Vest4		0.32
MVP		0.42
ClinPred		0.95	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.54
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

dbSNP: rs12487736; hg19: chr3-47459679;