22-31100540-T-C

Variant names:

• chr22-31100540-T-C
• rs56095120
• NM_134269.3:c.2604-345T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_134269.3(SMTN):​c.2604-345T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SMTN NM_134269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605
• Publications: 4 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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMTN	NM_134269.3	MANE Select	c.2604-345T>C		intron	N/A	NP_599031.1
	SMTN	NM_001382642.1		c.2886-345T>C		intron	N/A	NP_001369571.1
	SMTN	NM_001207017.1		c.2858+644T>C		intron	N/A	NP_001193946.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMTN	ENST00000333137.12	TSL:1 MANE Select	c.2604-345T>C		intron	N/A	ENSP00000329532.7
	SMTN	ENST00000347557.6	TSL:1	c.2603+644T>C		intron	N/A	ENSP00000328635.5
	SMTN	ENST00000619644.5	TSL:2	c.2858+644T>C		intron	N/A	ENSP00000484398.1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.78
PhyloP100		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

Other links and lift over

dbSNP: rs56095120; hg19: chr22-31496526;