22-31090305-G-C

Position:

• chr22-31090305-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000333137.12(SMTN):​c.865+125G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 723,646 control chromosomes in the GnomAD database, including 9,345 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 0.16 (2449 hom., cov: 31)
  • Exomes 𝑓: 0.13 (6896 hom.)
• Consequence: SMTN ENST00000333137.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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 (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMTN	NM_134269.3	c.865+125G>C		intron_variant		ENST00000333137.12	NP_599031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMTN	ENST00000333137.12	c.865+125G>C		intron_variant		1	NM_134269.3	ENSP00000329532	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23942 AN: 151242 Hom.: 2447 Cov.: 31

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0899

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.130 AC: 74533 AN: 572286 Hom.: 6896 AF XY: 0.129 AC XY: 38228 AN XY: 296752

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.0879

Gnomad4 ASJ exome AF: 0.0524

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.158 AC: 23963 AN: 151360 Hom.: 2449 Cov.: 31 AF XY: 0.156 AC XY: 11516 AN XY: 73926

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.0897

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.131

Alfa AF: 0.143 Hom.: 237

Bravo AF: 0.163

Asia WGS AF: 0.269 AC: 937 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	1.2
DANN	Benign	0.55

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: rs2074738; hg19: chr22-31486291; COSMIC: COSV60777653; COSMIC: COSV60777653;