Variant 22-31088086-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_134269.3(SMTN):c.173G>A(p.Arg58Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000772 in 1,607,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

SMTN
NM_134269.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37

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:

SMTN (HGNC:):

SMTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15305853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMTN	NM_134269.3 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	3/21	ENST00000333137.12	NP_599031.1	P53814-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMTN	ENST00000333137.12 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	3/21	1	NM_134269.3	ENSP00000329532.7		P53814-5

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000134

AC:

AN:

246274

Hom.:

AF XY:

0.000135

AC XY:

AN XY:

133592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000441

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.000142

Gnomad NFE exome

AF:

0.000180

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000749

AC:

109

AN:

1455056

Hom.:

Cov.:

AF XY:

0.0000830

AC XY:

AN XY:

722936

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000354

Gnomad4 SAS exome

AF:

0.0000583

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.0000704

Gnomad4 OTH exome

AF:

0.0000999

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000989

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2022

The c.335G>A (p.R112Q) alteration is located in exon 3 (coding exon 3) of the SMTN gene. This alteration results from a G to A substitution at nucleotide position 335, causing the arginine (R) at amino acid position 112 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

.;.;.;T;.;.;.;T;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

T;T;T;T;T;T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.15

T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.062

MutationAssessor

Benign

0.81

.;.;L;L;L;.;.;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.9

D;D;N;N;N;.;.;.;D

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;D;D;D;D;.;.;.;D

Sift4G

Uncertain

0.028

D;D;D;D;D;D;D;D;D

Polyphen

1.0

.;.;.;D;D;.;.;.;.

Vest4

0.27, 0.30, 0.27, 0.35, 0.31

MutPred

0.16

.;.;Loss of MoRF binding (P = 0.0398);Loss of MoRF binding (P = 0.0398);Loss of MoRF binding (P = 0.0398);Loss of MoRF binding (P = 0.0398);.;.;.;

MVP

0.48

MPC

0.72

ClinPred

0.21

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.28

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over