20-63643872-T-C

Variant names:

• chr20-63643872-T-C
• NM_015894.4:c.175A>G

Variant summary

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

The NM_015894.4(STMN3):​c.175A>G​(p.Lys59Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STMN3 NM_015894.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.11

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]

ACMG classification

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	c.175A>G	p.Lys59Glu	missense_variant	Exon 3 of 5	ENST00000370053.3	NP_056978.2
STMN3	NM_001276310.2	c.142A>G	p.Lys48Glu	missense_variant	Exon 3 of 5		NP_001263239.1
STMN3	NR_075070.2	n.254A>G		non_coding_transcript_exon_variant	Exon 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STMN3	ENST00000370053.3	c.175A>G	p.Lys59Glu	missense_variant	Exon 3 of 5	1	NM_015894.4	ENSP00000359070.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.175A>G (p.K59E) alteration is located in exon 3 (coding exon 3) of the STMN3 gene. This alteration results from a A to G substitution at nucleotide position 175, causing the lysine (K) at amino acid position 59 to be replaced by a glutamic acid (E). 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	0.55
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;.;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.5	.;M;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.0	D;D;.;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.0090	D;D;.;.
Sift4G	Benign	0.14	T;T;D;D
Polyphen		0.96	.;D;.;.
Vest4		0.40
MutPred		0.42		.;Loss of methylation at K59 (P = 9e-04);.;.;
MVP		0.56
MPC		2.0
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.51
gMVP		0.45

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: chr20-62275225;