rs56095120

chr22-31100540-T-Achr22-31100540-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_134269.3(SMTN):c.2604-345T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 147,182 control chromosomes in the GnomAD database, including 112 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 0.033 (112 hom., cov: 30)
• Consequence: SMTN NM_134269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605

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=-0.27).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0334 (4920/147182) while in subpopulation EAS AF= 0.0439 (209/4766). AF 95% confidence interval is 0.0404. There are 112 homozygotes in gnomad4. There are 2485 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 112 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMTN	NM_134269.3	c.2604-345T>A		intron_variant		ENST00000333137.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMTN	ENST00000333137.12	c.2604-345T>A		intron_variant		1	NM_134269.3	P1

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 4927 AN: 147070 Hom.: 112 Cov.: 30

Gnomad AFR AF: 0.00708

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0440

Gnomad SAS AF: 0.0233

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.0130

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.0323

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

GnomAD4 genome AF: 0.0334 AC: 4920 AN: 147182 Hom.: 112 Cov.: 30 AF XY: 0.0346 AC XY: 2485 AN XY: 71746

Gnomad4 AFR AF: 0.00706

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.0439

Gnomad4 SAS AF: 0.0227

Gnomad4 FIN AF: 0.0720

Gnomad4 NFE AF: 0.0417

Gnomad4 OTH AF: 0.0315

Alfa AF: 0.0356 Hom.: 20

Bravo AF: 0.0299

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	18
Dann	Benign	0.86

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: rs56095120; hg19: chr22-31496526;