12-15882777-G-C

Variant names:

• chr12-15882777-G-C
• NM_007178.4:c.70G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007178.4(STRAP):​c.70G>C​(p.Gly24Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 6.22
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.70G>C	p.Gly24Arg	missense	Exon 1 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.70G>C	p.Gly24Arg	missense	Exon 1 of 10	ENSP00000392270.2	Q9Y3F4-1
	STRAP	ENST00000025399.10	TSL:2	c.70G>C	p.Gly24Arg	missense	Exon 1 of 11	ENSP00000025399.6	Q9Y3F4-2
	STRAP	ENST00000888770.1		c.70G>C	p.Gly24Arg	missense	Exon 1 of 10	ENSP00000558829.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Benign	0.24
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.050
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.69	N
PhyloP100		6.2
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.18
Sift	Benign	0.24	T
Sift4G	Benign	0.55	T
Polyphen		0.036	B
Vest4		0.65
MutPred		0.33		Loss of glycosylation at S23 (P = 0.0493)
MVP		0.86
MPC		0.87
ClinPred		0.94	D
GERP RS		5.4
PromoterAI		0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.29
gMVP		0.72
Mutation Taster		=69/31	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

hg19: chr12-16035711;