chr12-15894132-C-A

Variant names:

• chr12-15894132-C-A
• rs1948040481
• NM_007178.4:c.489C>A

Variant summary

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

The NM_007178.4(STRAP):​c.489C>A​(p.Asp163Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STRAP NM_007178.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.686
• Publications: 0 publications found

Genes affected

STRAP (HGNC:30796): (serine/threonine kinase receptor associated protein) Enables RNA binding activity. Involved in maintenance of gastrointestinal epithelium; negative regulation of transforming growth factor beta receptor signaling pathway; and spliceosomal snRNP assembly. Located in cytosol. Part of SMN complex. Implicated in adenocarcinoma; colorectal carcinoma; large cell carcinoma; lung carcinoma; and squamous cell neoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.40241516).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007178.4. 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
	STRAP	NM_007178.4	MANE Select	c.489C>A	p.Asp163Glu	missense	Exon 5 of 10	NP_009109.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRAP	ENST00000419869.7	TSL:1 MANE Select	c.489C>A	p.Asp163Glu	missense	Exon 5 of 10	ENSP00000392270.2	Q9Y3F4-1
	STRAP	ENST00000025399.10	TSL:2	c.528C>A	p.Asp176Glu	missense	Exon 6 of 11	ENSP00000025399.6	Q9Y3F4-2
	STRAP	ENST00000888770.1		c.489C>A	p.Asp163Glu	missense	Exon 5 of 10	ENSP00000558829.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.69
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.50
Sift	Benign	0.030	D
Sift4G	Uncertain	0.048	D
Polyphen		0.91	P
Vest4		0.52
MutPred		0.50		Gain of ubiquitination at K177 (P = 0.0743)
MVP		0.67
MPC		0.76
ClinPred		0.97	D
GERP RS		1.8
Varity_R		0.38
gMVP		0.70
Mutation Taster		=71/29	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

dbSNP: rs1948040481; hg19: chr12-16047066;