Variant 7-129212147-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005631.5(SMO):c.2060C>T(p.Pro687Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000422 in 1,557,082 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

SMO
NM_005631.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 0.706

Variant links:

Genes affected

SMO (HGNC:11119): (smoothened, frizzled class receptor) The protein encoded by this gene is a G protein-coupled receptor that interacts with the patched protein, a receptor for hedgehog proteins. The encoded protein tranduces signals to other proteins after activation by a hedgehog protein/patched protein complex. [provided by RefSeq, Jul 2010]

SMO links:

ENSG00000243230 (HGNC:):

ENSG00000243230 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004938185).

BP6

Variant 7-129212147-C-T is Benign according to our data. Variant chr7-129212147-C-T is described in ClinVar as [Benign]. Clinvar id is 135259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00207 (315/152302) while in subpopulation AFR AF= 0.00719 (299/41574). AF 95% confidence interval is 0.00652. There are 2 homozygotes in gnomad4. There are 154 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 SM gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMO	NM_005631.5 linkuse as main transcript	c.2060C>T	p.Pro687Leu	missense_variant	12/12	ENST00000249373.8	NP_005622.1	Q99835
SMO	XM_047420759.1 linkuse as main transcript	c.1670C>T	p.Pro557Leu	missense_variant	13/13		XP_047276715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMO	ENST00000249373.8 linkuse as main transcript	c.2060C>T	p.Pro687Leu	missense_variant	12/12	1	NM_005631.5	ENSP00000249373.3		Q99835

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

310

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00709

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000550

AC:

AN:

161682

Hom.:

AF XY:

0.000430

AC XY:

AN XY:

86026

show subpopulations

Gnomad AFR exome

AF:

0.00856

Gnomad AMR exome

AF:

0.000356

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000860

Gnomad SAS exome

AF:

0.0000427

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000156

Gnomad OTH exome

AF:

0.000440

GnomAD4 exome

AF:

0.000243

AC:

342

AN:

1404780

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

149

AN XY:

693656

show subpopulations

Gnomad4 AFR exome

AF:

0.00842

Gnomad4 AMR exome

AF:

0.000466

Gnomad4 ASJ exome

AF:

0.0000396

Gnomad4 EAS exome

AF:

0.0000277

Gnomad4 SAS exome

AF:

0.0000500

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000129

Gnomad4 OTH exome

AF:

0.000635

GnomAD4 genome

AF:

0.00207

AC:

315

AN:

152302

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

154

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00719

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.00283

ESP6500AA

AF:

0.00902

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.000537

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Uncertain

0.61

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.72

M_CAP

Benign

0.051

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

REVEL

Benign

0.22

Sift

Benign

0.11

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.24

MVP

0.63

MPC

0.069

ClinPred

0.016

GERP RS

4.7

Varity_R

0.053

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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