rs9621187

chr22-31103532-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SMTN	NM_134269.3	c.*21-784A>G		intron_variant		ENST00000333137.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMTN	ENST00000333137.12	c.*21-784A>G		intron_variant		1	NM_134269.3	P1

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

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.750

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

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.409

Alfa AF: 0.374 Hom.: 3414

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9621187; hg19: chr22-31499518;