chr20-49115816-C-G

Variant names:

• chr20-49115816-C-G
• rs146411108
• NM_017453.4:c.1684G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017453.4(STAU1):​c.1684G>C​(p.Glu562Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E562K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: STAU1 NM_017453.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2781167).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017453.4. 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
	STAU1	NM_017453.4	MANE Select	c.1684G>C	p.Glu562Gln	missense	Exon 13 of 14	NP_059347.2	O95793-1
	STAU1	NM_001322932.2		c.1702G>C	p.Glu568Gln	missense	Exon 12 of 13	NP_001309861.1
	STAU1	NM_001322933.2		c.1702G>C	p.Glu568Gln	missense	Exon 13 of 14	NP_001309862.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAU1	ENST00000371856.7	TSL:1 MANE Select	c.1684G>C	p.Glu562Gln	missense	Exon 13 of 14	ENSP00000360922.2	O95793-1
	STAU1	ENST00000371828.7	TSL:1	c.1459G>C	p.Glu487Gln	missense	Exon 12 of 13	ENSP00000360893.3	O95793-3
	STAU1	ENST00000347458.9	TSL:1	c.1441G>C	p.Glu481Gln	missense	Exon 11 of 12	ENSP00000323443.7	O95793-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251474 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461816 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727204

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111972

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		7.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.26
Sift	Benign	0.062	T
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.53
MutPred		0.12		Loss of phosphorylation at S560 (P = 0.1375)
MVP		0.21
MPC		0.91
ClinPred		0.61	D
GERP RS		6.0
Varity_R		0.13
gMVP		0.32
Mutation Taster		=70/30	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

dbSNP: rs146411108; hg19: chr20-47732353;