rs761900618

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015894.4(STMN3):​c.143G>C​(p.Arg48Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,446,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R48Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

STMN3
NM_015894.4 missense

Scores

6
10
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.75
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.839

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STMN3NM_015894.4 linkc.143G>C p.Arg48Pro missense_variant Exon 3 of 5 ENST00000370053.3 NP_056978.2 Q9NZ72-1
STMN3NM_001276310.2 linkc.110G>C p.Arg37Pro missense_variant Exon 3 of 5 NP_001263239.1 Q9NZ72-2
STMN3NR_075070.2 linkn.222G>C non_coding_transcript_exon_variant Exon 3 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STMN3ENST00000370053.3 linkc.143G>C p.Arg48Pro missense_variant Exon 3 of 5 1 NM_015894.4 ENSP00000359070.1 Q9NZ72-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.92e-7
AC:
1
AN:
1446046
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
719692
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:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.38
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.38
.;T;T;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D;D;.;D
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.84
D;D;D;D
MetaSVM
Uncertain
-0.11
T
MutationAssessor
Uncertain
2.7
.;M;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-5.8
D;D;.;.
REVEL
Uncertain
0.41
Sift
Benign
0.043
D;D;.;.
Sift4G
Uncertain
0.038
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.95
MutPred
0.66
.;Loss of helix (P = 0.0376);.;.;
MVP
0.65
MPC
2.3
ClinPred
0.99
D
GERP RS
4.2
Varity_R
0.83
gMVP
0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-62275257; API