rs761900618

Variant names:

• chr20-63643904-C-G
• NM_015894.4:c.143G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-63643904-C-G
• chr20-63643904-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.75

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 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
STMN3	NM_015894.4	c.143G>C	p.Arg48Pro	missense_variant	Exon 3 of 5	ENST00000370053.3	NP_056978.2
STMN3	NM_001276310.2	c.110G>C	p.Arg37Pro	missense_variant	Exon 3 of 5		NP_001263239.1
STMN3	NR_075070.2	n.222G>C		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.143G>C	p.Arg48Pro	missense_variant	Exon 3 of 5	1	NM_015894.4	ENSP00000359070.1

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

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;