20-63642257-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015894.4(STMN3):​c.334G>A​(p.Glu112Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,545,716 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

STMN3
NM_015894.4 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.64
Variant links:
Genes affected
STMN3 (HGNC:15926): (stathmin 3) This gene encodes a protein which is a member of the stathmin protein family. Members of this protein family form a complex with tubulins at a ratio of 2 tubulins for each stathmin protein. Microtubules require the ordered assembly of alpha- and beta-tubulins, and formation of a complex with stathmin disrupts microtubule formation and function. A pseudogene of this gene is located on chromosome 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STMN3NM_015894.4 linkc.334G>A p.Glu112Lys missense_variant Exon 4 of 5 ENST00000370053.3 NP_056978.2 Q9NZ72-1
STMN3NM_001276310.2 linkc.301G>A p.Glu101Lys missense_variant Exon 4 of 5 NP_001263239.1 Q9NZ72-2
STMN3NR_075070.2 linkn.510G>A non_coding_transcript_exon_variant Exon 4 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STMN3ENST00000370053.3 linkc.334G>A p.Glu112Lys missense_variant Exon 4 of 5 1 NM_015894.4 ENSP00000359070.1 Q9NZ72-1
STMN3ENST00000631920.1 linkc.508G>A p.Glu170Lys missense_variant Exon 4 of 5 2 ENSP00000487795.1 A0A0J9YW36
STMN3ENST00000540534.5 linkc.301G>A p.Glu101Lys missense_variant Exon 4 of 5 2 ENSP00000439840.1 Q9NZ72-2

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151670
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
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:
0.0000295
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000466
AC:
9
AN:
193334
Hom.:
0
AF XY:
0.0000557
AC XY:
6
AN XY:
107798
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000275
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:
0.0000224
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000230
AC:
32
AN:
1394046
Hom.:
0
Cov.:
35
AF XY:
0.0000231
AC XY:
16
AN XY:
693420
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
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:
0.0000222
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151670
Hom.:
0
Cov.:
30
AF XY:
0.0000270
AC XY:
2
AN XY:
74056
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000295
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000830
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 18, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.334G>A (p.E112K) alteration is located in exon 4 (coding exon 4) of the STMN3 gene. This alteration results from a G to A substitution at nucleotide position 334, causing the glutamic acid (E) at amino acid position 112 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
0.44
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.27
.;T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Benign
0.62
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Uncertain
0.23
D
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Uncertain
-0.093
T
MutationAssessor
Uncertain
2.7
.;M
PrimateAI
Pathogenic
0.85
D
PROVEAN
Uncertain
-3.2
D;D
REVEL
Benign
0.21
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.023
D;D
Polyphen
1.0
.;D
Vest4
0.73
MVP
0.48
MPC
1.6
ClinPred
0.76
D
GERP RS
5.1
Varity_R
0.64
gMVP
0.81

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: rs370557606; hg19: chr20-62273610; COSMIC: COSV64246814; COSMIC: COSV64246814; API