dbSNP rs761900618: STMN3:p.Arg48Pro (chr20-63643904-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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 𝑓: 6.9e-7 ( 0 hom. )

Consequence

STMN3
NM_015894.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.75

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.839

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015894.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STMN3	NM_015894.4	MANE Select	c.143G>C	p.Arg48Pro	missense	Exon 3 of 5	NP_056978.2
STMN3	NM_001276310.2		c.110G>C	p.Arg37Pro	missense	Exon 3 of 5	NP_001263239.1	Q9NZ72-2
STMN3	NR_075070.2		n.222G>C		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STMN3	ENST00000370053.3	TSL:1 MANE Select	c.143G>C	p.Arg48Pro	missense	Exon 3 of 5	ENSP00000359070.1	Q9NZ72-1
STMN3	ENST00000631920.1	TSL:2	c.317G>C	p.Arg106Pro	missense	Exon 3 of 5	ENSP00000487795.1	A0A0J9YW36
STMN3	ENST00000860150.1		c.167G>C	p.Arg56Pro	missense	Exon 3 of 5	ENSP00000530209.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1446046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719692

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32248

American (AMR)

AF:

0.00

AC:

AN:

38956

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25332

East Asian (EAS)

AF:

0.00

AC:

AN:

39582

South Asian (SAS)

AF:

0.00

AC:

AN:

83938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108044

Other (OTH)

AF:

0.00

AC:

AN:

59746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.84

MetaSVM

Uncertain

-0.11

MutationAssessor

Uncertain

2.7

PhyloP100

7.8

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.8

REVEL

Uncertain

0.41

Sift

Benign

0.043

Sift4G

Uncertain

0.038

Polyphen

1.0

Vest4

0.95

MutPred

0.66

Loss of helix (P = 0.0376)

MVP

0.65

MPC

2.3

ClinPred

0.99

GERP RS

4.2

Varity_R

0.83

gMVP

0.60

Mutation Taster

=33/67

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over