NM_134269.3:c.5_6delCGinsAA

Variant names:

• chr22-31083263-CG-AA
• NM_134269.3:c.5_6delCGinsAA
• SMTN p.Ala2Glu

Variant summary

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

The NM_134269.3(SMTN):​c.5_6delCGinsAA​(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. A2V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMTN NM_134269.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 0 publications found

Genes affected

SMTN (HGNC:11126): (smoothelin) This gene encodes a structural protein that is found exclusively in contractile smooth muscle cells. It associates with stress fibers and constitutes part of the cytoskeleton. This gene is localized to chromosome 22q12.3, distal to the TUPLE1 locus and outside the DiGeorge syndrome deletion. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2011]

ENSG00000273387 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134269.3. 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
	SMTN	NM_134269.3	MANE Select	c.5_6delCGinsAA	p.Ala2Glu	missense	N/A	NP_599031.1	P53814-5
	SMTN	NM_001382642.1		c.287_288delCGinsAA	p.Ala96Glu	missense	N/A	NP_001369571.1
	SMTN	NM_001207017.1		c.167_168delCGinsAA	p.Ala56Glu	missense	N/A	NP_001193946.1	A0A087X1R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMTN	ENST00000333137.12	TSL:1 MANE Select	c.5_6delCGinsAA	p.Ala2Glu	missense	N/A	ENSP00000329532.7	P53814-5
	SMTN	ENST00000347557.6	TSL:1	c.5_6delCGinsAA	p.Ala2Glu	missense	N/A	ENSP00000328635.5	P53814-1
	SMTN	ENST00000619644.5	TSL:2	c.167_168delCGinsAA	p.Ala56Glu	missense	N/A	ENSP00000484398.1	A0A087X1R1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-31479249;