Variant 22-31087998-C-T 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.85C>T(p.Arg29Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,455,100 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: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SMTN
NM_134269.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

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 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=0.25135952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMTN	NM_134269.3 link	c.85C>T	p.Arg29Cys	missense_variant	Exon 3 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.85C>T	p.Arg29Cys	missense_variant	Exon 3 of 21	1	NM_134269.3	ENSP00000329532.7		P53814-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000813

AC:

AN:

246056

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000551

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1455100

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722756

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000825

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.247C>T (p.R83C) alteration is located in exon 3 (coding exon 3) of the SMTN gene. This alteration results from a C to T substitution at nucleotide position 247, causing the arginine (R) at amino acid position 83 to be replaced by a cysteine (C). 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

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.078

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

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.069

MetaRNN

Benign

0.25

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

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.69

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

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-6.5

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

REVEL

Benign

0.16

Sift

Uncertain

0.0010

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

Sift4G

Pathogenic

0.0

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

Polyphen

1.0

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

Vest4

0.47, 0.45, 0.43, 0.44, 0.42

MutPred

0.21

.;Loss of MoRF binding (P = 0.0626);.;.;Loss of MoRF binding (P = 0.0626);Loss of MoRF binding (P = 0.0626);Loss of MoRF binding (P = 0.0626);Loss of MoRF binding (P = 0.0626);.;.;.;

MVP

0.26

MPC

0.57

ClinPred

0.95

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.36

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