20-49118357-C-T

Variant names:

• chr20-49118357-C-T
• NM_017453.4:c.1165G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017453.4(STAU1):​c.1165G>A​(p.Gly389Ser) 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. 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)
• Consequence: STAU1 NM_017453.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48

Genes affected

STAU1 (HGNC:11370): (staufen double-stranded RNA binding protein 1) Staufen is a member of the family of double-stranded RNA (dsRNA)-binding proteins involved in the transport and/or localization of mRNAs to different subcellular compartments and/or organelles. These proteins are characterized by the presence of multiple dsRNA-binding domains which are required to bind RNAs having double-stranded secondary structures. The human homologue of staufen encoded by STAU, in addition contains a microtubule- binding domain similar to that of microtubule-associated protein 1B, and binds tubulin. The STAU gene product has been shown to be present in the cytoplasm in association with the rough endoplasmic reticulum (RER), implicating this protein in the transport of mRNA via the microtubule network to the RER, the site of translation. [provided by RefSeq, Apr 2020]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06661326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAU1	NM_017453.4	c.1165G>A	p.Gly389Ser	missense_variant	Exon 10 of 14	ENST00000371856.7	NP_059347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAU1	ENST00000371856.7	c.1165G>A	p.Gly389Ser	missense_variant	Exon 10 of 14	1	NM_017453.4	ENSP00000360922.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1165G>A (p.G389S) alteration is located in exon 10 (coding exon 8) of the STAU1 gene. This alteration results from a G to A substitution at nucleotide position 1165, causing the glycine (G) at amino acid position 389 to be replaced by a serine (S). 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	0.066
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.079	T;.;.;.;.;.;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.84	T;T;.;.;T;.;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.067	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.83	L;.;.;.;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.22	N;N;N;N;N;N;N
REVEL	Benign	0.049
Sift	Benign	0.55	T;T;T;T;T;T;T
Sift4G	Benign	0.67	T;T;T;T;T;T;T
Polyphen		0.0010	B;.;.;.;.;.;.
Vest4		0.12
MutPred		0.26		Gain of glycosylation at G389 (P = 0.0269);.;.;.;.;.;.;
MVP		0.22
MPC		0.45
ClinPred		0.12	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr20-47734894;