rs10304

Positions:

• chr22-31104550-G-A
• chr22-31104550-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_134269.3(SMTN):​c.*255G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,417,390 control chromosomes in the GnomAD database, including 16,909 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 0.13 (1767 hom., cov: 32)
  • Exomes 𝑓: 0.13 (15142 hom.)
• Consequence: SMTN NM_134269.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.905

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMTN	NM_134269.3	c.*255G>A		3_prime_UTR_variant	21/21	ENST00000333137.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMTN	ENST00000333137.12	c.*255G>A		3_prime_UTR_variant	21/21	1	NM_134269.3	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19661 AN: 151982 Hom.: 1773 Cov.: 32

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.132 AC: 167485 AN: 1265290 Hom.: 15142 Cov.: 18 AF XY: 0.136 AC XY: 86600 AN XY: 634488

Gnomad4 AFR exome AF: 0.0478

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.433

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.129 AC: 19657 AN: 152100 Hom.: 1767 Cov.: 32 AF XY: 0.139 AC XY: 10302 AN XY: 74352

Gnomad4 AFR AF: 0.0552

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.139

Alfa AF: 0.117 Hom.: 1795

Bravo AF: 0.127

Asia WGS AF: 0.322 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.95

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: rs10304; hg19: chr22-31500536; COSMIC: COSV60778809; COSMIC: COSV60778809;