14-30895518-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001083893.2(STRN3):​c.2287G>T​(p.Ala763Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

STRN3
NM_001083893.2 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86
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]
COCH (HGNC:2180): (cochlin) The protein encoded by this gene is highly conserved in human, mouse, and chicken, showing 94% and 79% amino acid identity of human to mouse and chicken sequences, respectively. Hybridization to this gene was detected in spindle-shaped cells located along nerve fibers between the auditory ganglion and sensory epithelium. These cells accompany neurites at the habenula perforata, the opening through which neurites extend to innervate hair cells. This and the pattern of expression of this gene in chicken inner ear paralleled the histologic findings of acidophilic deposits, consistent with mucopolysaccharide ground substance, in temporal bones from DFNA9 (autosomal dominant nonsyndromic sensorineural deafness 9) patients. Mutations that cause DFNA9 have been reported in this gene. Alternative splicing results in multiple transcript variants encoding the same protein. Additional splice variants encoding distinct isoforms have been described but their biological validities have not been demonstrated. [provided by RefSeq, Oct 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.28952).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STRN3NM_001083893.2 linkc.2287G>T p.Ala763Ser missense_variant Exon 18 of 18 ENST00000357479.10 NP_001077362.1 Q13033-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STRN3ENST00000357479.10 linkc.2287G>T p.Ala763Ser missense_variant Exon 18 of 18 5 NM_001083893.2 ENSP00000350071.5 Q13033-1
STRN3ENST00000355683.9 linkc.2035G>T p.Ala679Ser missense_variant Exon 16 of 16 1 ENSP00000347909.5 Q13033-2
STRN3ENST00000555358.5 linkn.*902G>T non_coding_transcript_exon_variant Exon 15 of 15 1 ENSP00000451028.1 G3V340
STRN3ENST00000555358.5 linkn.*902G>T 3_prime_UTR_variant Exon 15 of 15 1 ENSP00000451028.1 G3V340

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000119
AC:
30
AN:
251208
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135764
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000868
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000315
AC:
46
AN:
1461748
Hom.:
0
Cov.:
31
AF XY:
0.0000275
AC XY:
20
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000962
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:
0.0000497
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000117
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2287G>T (p.A763S) alteration is located in exon 18 (coding exon 18) of the STRN3 gene. This alteration results from a G to T substitution at nucleotide position 2287, causing the alanine (A) at amino acid position 763 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
0.24
BayesDel_addAF
Benign
-0.042
T
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.047
.;T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Uncertain
0.16
D
MutationAssessor
Benign
0.98
.;L
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-1.9
N;N
REVEL
Pathogenic
0.68
Sift
Benign
0.12
T;T
Sift4G
Benign
0.12
T;T
Polyphen
0.51
P;D
Vest4
0.56
MutPred
0.62
.;Gain of catalytic residue at L768 (P = 2e-04);
MVP
0.88
MPC
0.54
ClinPred
0.19
T
GERP RS
5.5
Varity_R
0.20
gMVP
0.31

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: rs779186622; hg19: chr14-31364724; API