rs5753454

Variant names:

• chr22-31079321-G-A
• rs5753454
• NM_001382642.1:c.-194-1129G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382642.1(SMTN):​c.-194-1129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,238 control chromosomes in the GnomAD database, including 4,114 homozygotes. 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: 𝑓 0.21 (4114 hom., cov: 33)
• Consequence: SMTN NM_001382642.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.550
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMTN	NM_001382642.1	c.-194-1129G>A		intron_variant	Intron 1 of 22		NP_001369571.1
SMTN	NM_001382643.1	c.-204-1129G>A		intron_variant	Intron 1 of 23		NP_001369572.1
SMTN	NM_001382645.1	c.-385-1129G>A		intron_variant	Intron 1 of 22		NP_001369574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMTN	ENST00000432777.5	c.-210-1129G>A		intron_variant	Intron 1 of 5	3		ENSP00000398663.1
SMTN	ENST00000422839.5	c.-385-1129G>A		intron_variant	Intron 1 of 3	4		ENSP00000390453.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31927 AN: 152120 Hom.: 4111 Cov.: 33

Gnomad AFR AF: 0.0755

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.210 AC: 31936 AN: 152238 Hom.: 4114 Cov.: 33 AF XY: 0.219 AC XY: 16323 AN XY: 74422

African (AFR) AF: 0.0753 AC: 3131 AN: 41566

American (AMR) AF: 0.316 AC: 4823 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2268 AN: 5172

South Asian (SAS) AF: 0.304 AC: 1468 AN: 4830

European-Finnish (FIN) AF: 0.317 AC: 3358 AN: 10588

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15426 AN: 68010

Other (OTH) AF: 0.201 AC: 424 AN: 2114

Alfa AF: 0.223 Hom.: 2180

Bravo AF: 0.201

Asia WGS AF: 0.342 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.50
PhyloP100		0.55

Splicing

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

Other links and lift over

dbSNP: rs5753454; hg19: chr22-31475307;