20-63642257-C-A

Variant names:

• chr20-63642257-C-A
• rs370557606
• NM_015894.4:c.334G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015894.4(STMN3):​c.334G>T​(p.Glu112*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,046 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: STMN3 NM_015894.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.64
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STMN3	NM_015894.4	MANE Select	c.334G>T	p.Glu112*	stop_gained	Exon 4 of 5	NP_056978.2
	STMN3	NM_001276310.2		c.301G>T	p.Glu101*	stop_gained	Exon 4 of 5	NP_001263239.1	Q9NZ72-2
	STMN3	NR_075070.2		n.510G>T		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STMN3	ENST00000370053.3	TSL:1 MANE Select	c.334G>T	p.Glu112*	stop_gained	Exon 4 of 5	ENSP00000359070.1	Q9NZ72-1
	STMN3	ENST00000631920.1	TSL:2	c.508G>T	p.Glu170*	stop_gained	Exon 4 of 5	ENSP00000487795.1	A0A0J9YW36
	STMN3	ENST00000860150.1		c.358G>T	p.Glu120*	stop_gained	Exon 4 of 5	ENSP00000530209.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394046 Hom.: 0 Cov.: 35 AF XY: 0.00000144 AC XY: 1 AN XY: 693420

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28692

American (AMR) AF: 0.00 AC: 0 AN: 35744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24258

East Asian (EAS) AF: 0.00 AC: 0 AN: 31920

South Asian (SAS) AF: 0.00 AC: 0 AN: 80084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5466

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079980

Other (OTH) AF: 0.00 AC: 0 AN: 56946

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Benign	0.66	D
PhyloP100		7.6
Vest4		0.85
GERP RS		5.1
Mutation Taster		=47/153	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs370557606; hg19: chr20-62273610;