Genetic Variant SMTN:c.865+125G>C (chr22-31090305-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001382642.1(SMTN):c.1147+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
NM_001382642.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0290

Publications

6 publications found

Variant links:

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]

SMTN links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMTN	NM_134269.3	MANE Select	c.865+125G>C	intron	N/A	NP_599031.1
SMTN	NM_001382642.1		c.1147+125G>C	intron	N/A	NP_001369571.1
SMTN	NM_001207017.1		c.1027+125G>C	intron	N/A	NP_001193946.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMTN	ENST00000333137.12	TSL:1 MANE Select	c.865+125G>C	intron	N/A	ENSP00000329532.7
SMTN	ENST00000347557.6	TSL:1	c.865+125G>C	intron	N/A	ENSP00000328635.5
SMTN	ENST00000619644.5	TSL:2	c.1027+125G>C	intron	N/A	ENSP00000484398.1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

23942

AN:

151242

Hom.:

2447

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.265

AC:

3851

AN:

14538

American (AMR)

AF:

0.0879

AC:

1697

AN:

19302

Ashkenazi Jewish (ASJ)

AF:

0.0524

AC:

760

AN:

14514

East Asian (EAS)

AF:

0.441

AC:

14038

AN:

31838

South Asian (SAS)

AF:

0.114

AC:

5541

AN:

48604

European-Finnish (FIN)

AF:

0.118

AC:

4267

AN:

36226

Middle Eastern (MID)

AF:

0.0714

AC:

161

AN:

2254

European-Non Finnish (NFE)

AF:

0.107

AC:

40315

AN:

375148

Other (OTH)

AF:

0.131

AC:

3903

AN:

29862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3335

6670

10006

13341

16676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

804

1608

2412

3216

4020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.158

AC:

23963

AN:

151360

Hom.:

2449

Cov.:

AF XY:

0.156

AC XY:

11516

AN XY:

73926

show subpopulations

African (AFR)

AF:

0.265

AC:

10874

AN:

41098

American (AMR)

AF:

0.0897

AC:

1368

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

162

AN:

3470

East Asian (EAS)

AF:

0.435

AC:

2202

AN:

5064

South Asian (SAS)

AF:

0.113

AC:

544

AN:

4804

European-Finnish (FIN)

AF:

0.107

AC:

1127

AN:

10524

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7362

AN:

67844

Other (OTH)

AF:

0.131

AC:

274

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

893

1786

2678

3571

4464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.2

(source)

DANN

Benign

0.55

PhyloP100

0.029

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over