rs9621187

Variant names:

• chr22-31103532-A-G
• rs9621187
• NM_134269.3:c.*21-784A>G

Variant summary

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

The NM_134269.3(SMTN):​c.*21-784A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,200 control chromosomes in the GnomAD database, including 10,460 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 0.36 (10454 hom., cov: 33)
  • Exomes 𝑓: 0.43 (6 hom.)
• Consequence: SMTN NM_134269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMTN	NM_134269.3	c.*21-784A>G		intron_variant	Intron 20 of 20	ENST00000333137.12	NP_599031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMTN	ENST00000333137.12	c.*21-784A>G		intron_variant	Intron 20 of 20	1	NM_134269.3	ENSP00000329532.7

Frequencies

GnomAD3 genomes AF: 0.355 AC: 54016 AN: 151988 Hom.: 10450 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.426 AC: 40 AN: 94 Hom.: 6 Cov.: 0 AF XY: 0.438 AC XY: 28 AN XY: 64

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.436 AC: 34 AN: 78

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.355 AC: 54043 AN: 152106 Hom.: 10454 Cov.: 33 AF XY: 0.354 AC XY: 26349 AN XY: 74350

African (AFR) AF: 0.261 AC: 10829 AN: 41498

American (AMR) AF: 0.327 AC: 4999 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1803 AN: 3470

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5180

South Asian (SAS) AF: 0.464 AC: 2236 AN: 4814

European-Finnish (FIN) AF: 0.383 AC: 4052 AN: 10572

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.421 AC: 28623 AN: 67978

Other (OTH) AF: 0.409 AC: 863 AN: 2112

Alfa AF: 0.376 Hom.: 4370

Bravo AF: 0.344

Asia WGS AF: 0.237 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.74
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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: rs9621187; hg19: chr22-31499518;