Genetic Variant STMN3:p.Glu177Gly (chr20-63641351-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_015894.4(STMN3):c.530A>G(p.Glu177Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000212 in 1,416,166 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: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

STMN3
NM_015894.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.60

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]

STMN3 links:

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
STMN3	NM_015894.4 link	c.530A>G	p.Glu177Gly	missense_variant	Exon 5 of 5	ENST00000370053.3	NP_056978.2	Q9NZ72-1
STMN3	NM_001276310.2 link	c.497A>G	p.Glu166Gly	missense_variant	Exon 5 of 5		NP_001263239.1	Q9NZ72-2
STMN3	NR_075070.2 link	n.706A>G		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STMN3	ENST00000370053.3 link	c.530A>G	p.Glu177Gly	missense_variant	Exon 5 of 5	1	NM_015894.4	ENSP00000359070.1	Q9NZ72-1
STMN3	ENST00000631920.1 link	c.704A>G	p.Glu235Gly	missense_variant	Exon 5 of 5	2		ENSP00000487795.1	A0A0J9YW36
STMN3	ENST00000540534.5 link	c.497A>G	p.Glu166Gly	missense_variant	Exon 5 of 5	2		ENSP00000439840.1	Q9NZ72-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182908

Hom.:

AF XY:

0.0000102

AC XY:

AN XY:

98084

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1416166

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700524

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:

0.00000275

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.530A>G (p.E177G) alteration is located in exon 5 (coding exon 5) of the STMN3 gene. This alteration results from a A to G substitution at nucleotide position 530, causing the glutamic acid (E) at amino acid position 177 to be replaced by a glycine (G). 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

0.14

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

.;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.0

.;M

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.16

Sift

Benign

0.037

D;D

Sift4G

Benign

0.085

T;T

Polyphen

0.89

.;P

Vest4

0.27

MutPred

0.44

.;Gain of MoRF binding (P = 0.007);

MVP

0.42

MPC

1.3

ClinPred

0.56

GERP RS

4.9

Varity_R

0.39

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.24

Position offset: 46

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over