12-15894132-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40241516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRAP	NM_007178.4	c.489C>A	p.Asp163Glu	missense_variant	Exon 5 of 10	ENST00000419869.7	NP_009109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRAP	ENST00000419869.7	c.489C>A	p.Asp163Glu	missense_variant	Exon 5 of 10	1	NM_007178.4	ENSP00000392270.2
STRAP	ENST00000025399.10	c.528C>A	p.Asp176Glu	missense_variant	Exon 6 of 11	2		ENSP00000025399.6
STRAP	ENST00000541731.1	n.*206C>A		non_coding_transcript_exon_variant	Exon 4 of 9	2		ENSP00000445693.1
STRAP	ENST00000541731.1	n.*206C>A		3_prime_UTR_variant	Exon 4 of 9	2		ENSP00000445693.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.489C>A (p.D163E) alteration is located in exon 5 (coding exon 5) of the STRAP gene. This alteration results from a C to A substitution at nucleotide position 489, causing the aspartic acid (D) at amino acid position 163 to be replaced by a glutamic acid (E). 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	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;D
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	3.2	.;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.50
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.048	D;T
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

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

Other links and lift over

dbSNP: rs1948040481; hg19: chr12-16047066;