Genetic Variant STRAP:p.Ser153Arg (chr12-15894102-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007178.4(STRAP):c.459T>G(p.Ser153Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

STRAP
NM_007178.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

Variant links:

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]

STRAP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.106428385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRAP	NM_007178.4 link	c.459T>G	p.Ser153Arg	missense_variant	Exon 5 of 10	ENST00000419869.7	NP_009109.3	Q9Y3F4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STRAP	ENST00000419869.7 link	c.459T>G	p.Ser153Arg	missense_variant	Exon 5 of 10	1	NM_007178.4	ENSP00000392270.2	Q9Y3F4-1
STRAP	ENST00000025399.10 link	c.498T>G	p.Ser166Arg	missense_variant	Exon 6 of 11	2		ENSP00000025399.6	Q9Y3F4-2
STRAP	ENST00000541731.1 link	n.*176T>G		non_coding_transcript_exon_variant	Exon 4 of 9	2		ENSP00000445693.1	F5H1G1
STRAP	ENST00000541731.1 link	n.*176T>G		3_prime_UTR_variant	Exon 4 of 9	2		ENSP00000445693.1	F5H1G1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251308

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461358

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.459T>G (p.S153R) alteration is located in exon 5 (coding exon 5) of the STRAP gene. This alteration results from a T to G substitution at nucleotide position 459, causing the serine (S) at amino acid position 153 to be replaced by an arginine (R). 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

Benign

0.20

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.20

.;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.065

.;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.57

N;N

REVEL

Benign

0.10

Sift

Benign

0.53

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0

.;B

Vest4

0.28

MutPred

0.39

Gain of MoRF binding (P = 0.0333);.;

MVP

0.22

MPC

0.80

ClinPred

0.55

GERP RS

2.9

Varity_R

0.16

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over