20-49115816-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_017453.4(STAU1):​c.1684G>A​(p.Glu562Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

STAU1
NM_017453.4 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STAU1NM_017453.4 linkc.1684G>A p.Glu562Lys missense_variant Exon 13 of 14 ENST00000371856.7 NP_059347.2 O95793-1B3KRE0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STAU1ENST00000371856.7 linkc.1684G>A p.Glu562Lys missense_variant Exon 13 of 14 1 NM_017453.4 ENSP00000360922.2 O95793-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251474
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461816
Hom.:
0
Cov.:
30
AF XY:
0.0000151
AC XY:
11
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 02, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1684G>A (p.E562K) alteration is located in exon 13 (coding exon 11) of the STAU1 gene. This alteration results from a G to A substitution at nucleotide position 1684, causing the glutamic acid (E) at amino acid position 562 to be replaced by a lysine (K). 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
Uncertain
0.41
BayesDel_addAF
Benign
-0.024
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.054
T;T;.;.;.;.;.;T
Eigen
Uncertain
0.59
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D;D;.;.;D;.;D
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.44
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.90
L;.;.;.;.;.;.;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.88
N;.;N;N;N;N;N;N
REVEL
Benign
0.15
Sift
Uncertain
0.0070
D;.;D;D;D;D;D;D
Sift4G
Uncertain
0.022
D;D;D;D;D;D;D;D
Polyphen
0.97
D;.;.;.;.;.;.;.
Vest4
0.68
MVP
0.16
MPC
0.84
ClinPred
0.73
D
GERP RS
6.0
Varity_R
0.35
gMVP
0.37

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

LitVar

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

Other links and lift over

dbSNP: rs146411108; hg19: chr20-47732353; API