12-15882811-C-G

Variant names:

• chr12-15882811-C-G
• NM_007178.4:c.104C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007178.4(STRAP):​c.104C>G​(p.Ala35Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.40

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRAP	NM_007178.4	c.104C>G	p.Ala35Gly	missense_variant	Exon 1 of 10	ENST00000419869.7	NP_009109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRAP	ENST00000419869.7	c.104C>G	p.Ala35Gly	missense_variant	Exon 1 of 10	1	NM_007178.4	ENSP00000392270.2
STRAP	ENST00000025399.10	c.104C>G	p.Ala35Gly	missense_variant	Exon 1 of 11	2		ENSP00000025399.6
STRAP	ENST00000541731.1	n.98C>G		non_coding_transcript_exon_variant	Exon 1 of 9	2		ENSP00000445693.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.104C>G (p.A35G) alteration is located in exon 1 (coding exon 1) of the STRAP gene. This alteration results from a C to G substitution at nucleotide position 104, causing the alanine (A) at amino acid position 35 to be replaced by a glycine (G). 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	0.68
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	.;D
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Uncertain	-0.040	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.46
Sift	Benign	0.041	D;D
Sift4G	Benign	0.068	T;T
Polyphen		1.0	.;D
Vest4		0.54
MutPred		0.86		Loss of stability (P = 0.0652);Loss of stability (P = 0.0652);
MVP		0.79
MPC		0.84
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-16035745;