14-30906918-T-C

Variant summary

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

The NM_001083893.2(STRN3):​c.1847A>G​(p.Gln616Arg) 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

STRN3
NM_001083893.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32
Variant links:
Genes affected
STRN3 (HGNC:15720): (striatin 3) Enables armadillo repeat domain binding activity; protein phosphatase 2A binding activity; and small GTPase binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; nucleoplasm; and plasma membrane. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.19624332).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STRN3NM_001083893.2 linkuse as main transcriptc.1847A>G p.Gln616Arg missense_variant 14/18 ENST00000357479.10 NP_001077362.1 Q13033-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STRN3ENST00000357479.10 linkuse as main transcriptc.1847A>G p.Gln616Arg missense_variant 14/185 NM_001083893.2 ENSP00000350071.5 Q13033-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 12, 2024The c.1847A>G (p.Q616R) alteration is located in exon 14 (coding exon 14) of the STRN3 gene. This alteration results from a A to G substitution at nucleotide position 1847, causing the glutamine (Q) at amino acid position 616 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
0.072
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.027
.;T
Eigen
Benign
-0.13
Eigen_PC
Benign
0.048
FATHMM_MKL
Benign
0.76
D
LIST_S2
Benign
0.57
T;T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.48
T
MutationAssessor
Benign
0.97
.;L
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.95
N;N
REVEL
Benign
0.17
Sift
Benign
0.26
T;T
Sift4G
Benign
0.38
T;T
Polyphen
0.0010
B;B
Vest4
0.35
MutPred
0.44
.;Gain of catalytic residue at P620 (P = 2e-04);
MVP
0.81
MPC
0.14
ClinPred
0.42
T
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.12
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr14-31376124; API