12-15895490-C-T

Variant names:

• chr12-15895490-C-T
• rs1948052464
• NM_007178.4:c.632C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007178.4(STRAP):​c.632C>T​(p.Ala211Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,810 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: STRAP NM_007178.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.22

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRAP	NM_007178.4	c.632C>T	p.Ala211Val	missense_variant	Exon 6 of 10	ENST00000419869.7	NP_009109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRAP	ENST00000419869.7	c.632C>T	p.Ala211Val	missense_variant	Exon 6 of 10	1	NM_007178.4	ENSP00000392270.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443810 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 717520

Gnomad4 AFR exome AF: 0.0000311

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.632C>T (p.A211V) alteration is located in exon 6 (coding exon 6) of the STRAP gene. This alteration results from a C to T substitution at nucleotide position 632, causing the alanine (A) at amino acid position 211 to be replaced by a valine (V). 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	0.26
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	.;T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.26
Sift	Benign	0.17	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.14	.;B
Vest4		0.73
MutPred		0.31		Loss of sheet (P = 0.1158);.;
MVP		0.56
MPC		1.1
ClinPred		0.91	D
GERP RS		5.0
Varity_R		0.27
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1948052464; hg19: chr12-16048424;