22-31083236-C-G

Variant names:

• chr22-31083236-C-G
• rs765395165
• NM_134269.3:c.-23C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001382642.1(SMTN):​c.260C>G​(p.Pro87Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P87T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SMTN NM_001382642.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 0 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]

ENSG00000273387 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05146128).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382642.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMTN	NM_134269.3	MANE Select	c.-23C>G		5_prime_UTR	Exon 2 of 21	NP_599031.1	P53814-5
	SMTN	NM_001382642.1		c.260C>G	p.Pro87Arg	missense	Exon 4 of 23	NP_001369571.1
	SMTN	NM_001207017.1		c.140C>G	p.Pro47Arg	missense	Exon 2 of 21	NP_001193946.1	A0A087X1R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMTN	ENST00000333137.12	TSL:1 MANE Select	c.-23C>G		5_prime_UTR	Exon 2 of 21	ENSP00000329532.7	P53814-5
	SMTN	ENST00000347557.6	TSL:1	c.-23C>G		5_prime_UTR	Exon 2 of 20	ENSP00000328635.5	P53814-1
	SMTN	ENST00000619644.5	TSL:2	c.140C>G	p.Pro47Arg	missense	Exon 2 of 21	ENSP00000484398.1	A0A087X1R1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445136 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717122

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 40562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25706

East Asian (EAS) AF: 0.00 AC: 0 AN: 38998

South Asian (SAS) AF: 0.00 AC: 0 AN: 82924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5174

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106226

Other (OTH) AF: 0.00 AC: 0 AN: 59866

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.13
DANN	Benign	0.60
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.5
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.024
Sift	Uncertain	0.0090	D
Sift4G	Pathogenic	0.0	D
Vest4		0.13
MutPred		0.20		Loss of loop (P = 0.0022)
MVP		0.10
ClinPred		0.059	T
GERP RS		-5.7
PromoterAI		0.0016	Neutral
gMVP		0.092
Mutation Taster		=300/0	polymorphism

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: rs765395165; hg19: chr22-31479222;