chr22-31104550-G-A

Variant names:

• chr22-31104550-G-A
• rs10304
• NM_134269.3:c.*255G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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]

SELENOM (HGNC:30397): (selenoprotein M) The protein encoded by this gene belongs to the selenoprotein M/SEP15 family. The exact function of this protein is not known. It is localized in the perinuclear region, is highly expressed in the brain, and may be involved in neurodegenerative disorders. Transgenic mice with targeted deletion of this gene exhibit increased weight gain, suggesting a role for this gene in the regulation of body weight and energy metabolism. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMTN	NM_134269.3	c.*255G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000333137.12	NP_599031.1
SELENOM	NM_080430.4	c.*420C>T		downstream_gene_variant		ENST00000400299.6	NP_536355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMTN	ENST00000333137.12	c.*255G>A		3_prime_UTR_variant	Exon 21 of 21	1	NM_134269.3	ENSP00000329532.7
SELENOM	ENST00000400299.6	c.*420C>T		downstream_gene_variant		1	NM_080430.4	ENSP00000383155.2

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

African (AFR) AF: 0.0478 AC: 1427 AN: 29874

American (AMR) AF: 0.267 AC: 11444 AN: 42894

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 2909 AN: 23888

East Asian (EAS) AF: 0.433 AC: 16631 AN: 38384

South Asian (SAS) AF: 0.265 AC: 21206 AN: 79884

European-Finnish (FIN) AF: 0.170 AC: 6644 AN: 39156

Middle Eastern (MID) AF: 0.129 AC: 655 AN: 5080

European-Non Finnish (NFE) AF: 0.104 AC: 98896 AN: 952258

Other (OTH) AF: 0.142 AC: 7673 AN: 53872

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

African (AFR) AF: 0.0552 AC: 2291 AN: 41512

American (AMR) AF: 0.237 AC: 3623 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3472

East Asian (EAS) AF: 0.415 AC: 2136 AN: 5142

South Asian (SAS) AF: 0.269 AC: 1299 AN: 4824

European-Finnish (FIN) AF: 0.170 AC: 1802 AN: 10584

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7732 AN: 67966

Other (OTH) AF: 0.139 AC: 293 AN: 2110

Alfa AF: 0.117 Hom.: 2823

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
PhyloP100		0.91
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: rs10304; hg19: chr22-31500536; COSMIC: COSV60778809; COSMIC: COSV60778809;