Variant 22-31083296-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_134269.3(SMTN):c.38C>T(p.Ala13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000835 in 1,577,332 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 3 hom. )

Consequence

SMTN
NM_134269.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

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:

ENSG00000273387 (HGNC:):

ENSG00000273387 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02765435).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMTN	NM_134269.3 link	c.38C>T	p.Ala13Val	missense_variant	Exon 2 of 21	ENST00000333137.12	NP_599031.1	P53814-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMTN	ENST00000333137.12 link	c.38C>T	p.Ala13Val	missense_variant	Exon 2 of 21	1	NM_134269.3	ENSP00000329532.7		P53814-5

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000579

AC:

115

AN:

198490

Hom.:

AF XY:

0.000594

AC XY:

AN XY:

106020

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000173

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000404

GnomAD4 exome

AF:

0.000843

AC:

1201

AN:

1425042

Hom.:

Cov.:

AF XY:

0.000868

AC XY:

612

AN XY:

705180

show subpopulations

Gnomad4 AFR exome

AF:

0.000182

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000156

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.000627

GnomAD4 genome

AF:

0.000762

AC:

116

AN:

152290

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000842

Hom.:

Bravo

AF:

0.000740

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000411

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.200C>T (p.A67V) alteration is located in exon 2 (coding exon 2) of the SMTN gene. This alteration results from a C to T substitution at nucleotide position 200, causing the alanine (A) at amino acid position 67 to be replaced by a valine (V). 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

0.27

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.068

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

Eigen

Benign

0.059

Eigen_PC

Benign

0.019

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

D;D;D;T;T;T;T;D;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.028

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

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

.;.;.;.;N;N;N;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.3

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

REVEL

Benign

0.11

Sift

Uncertain

0.0090

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

Sift4G

Pathogenic

0.0

D;D;T;T;T;T;T;T;T

Polyphen

1.0, 0.99

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

Vest4

0.49, 0.59, 0.52, 0.70

MVP

0.043

MPC

0.67

ClinPred

0.057

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.13

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