Variant 11-57543205-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001105565.3(SMTNL1):c.563A>G(p.Glu188Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000302 in 1,613,810 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 3 hom. )

Consequence

SMTNL1
NM_001105565.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0540

Variant links:

Genes affected

SMTNL1 (HGNC:32394): (smoothelin like 1) The protein encoded by this gene is involved in the contraction of both striated and smooth muscle. During pregnancy, the encoded protein interacts with progesterone receptor to attenuate the expression of contractile and metabolic proteins. [provided by RefSeq, Jul 2016]

SMTNL1 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=0.017641872).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMTNL1	NM_001105565.3 linkuse as main transcript	c.563A>G	p.Glu188Gly	missense_variant	2/8	ENST00000527972.6	NP_001099035.2	A8MU46

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMTNL1	ENST00000527972.6 linkuse as main transcript	c.563A>G	p.Glu188Gly	missense_variant	2/8	5	NM_001105565.3	ENSP00000432651.1		A8MU46

Frequencies

GnomAD3 genomes

AF:

0.000362

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00649

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000369

AC:

AN:

248998

Hom.:

AF XY:

0.000385

AC XY:

AN XY:

135092

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000541

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000296

AC:

432

AN:

1461668

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

240

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000295

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000362

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000593

Hom.:

Bravo

AF:

0.000404

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000356

AC:

ExAC

AF:

0.000297

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000889

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

May 02, 2024

The c.563A>G (p.E188G) alteration is located in exon 1 (coding exon 1) of the SMTNL1 gene. This alteration results from a A to G substitution at nucleotide position 563, causing the glutamic acid (E) at amino acid position 188 to be replaced by a glycine (G). 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

0.067

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.33

M_CAP

Benign

0.0073

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.0

REVEL

Benign

0.016

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.015

Vest4

0.13

MVP

0.061

ClinPred

0.019

GERP RS

1.2

gMVP

0.067

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