Variant 7-129189225-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005631.5(SMO):c.74A>G(p.Asp25Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 1,160,946 control chromosomes in the GnomAD database, including 5,729 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1501 hom., cov: 32)

Exomes 𝑓: 0.089 ( 4228 hom. )

Consequence

SMO
NM_005631.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.268

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013649166).

BP6

Variant 7-129189225-A-G is Benign according to our data. Variant chr7-129189225-A-G is described in ClinVar as [Benign]. Clinvar id is 768202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMO	NM_005631.5 linkuse as main transcript	c.74A>G	p.Asp25Gly	missense_variant	1/12	ENST00000249373.8	NP_005622.1	Q99835
SMO	XM_047420759.1 linkuse as main transcript	c.-431A>G		5_prime_UTR_variant	1/13		XP_047276715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMO	ENST00000249373.8 linkuse as main transcript	c.74A>G	p.Asp25Gly	missense_variant	1/12	1	NM_005631.5	ENSP00000249373.3		Q99835
SMO	ENST00000655644.1 linkuse as main transcript	n.74A>G		non_coding_transcript_exon_variant	1/12			ENSP00000499377.1		A0A590UJE7

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18573

AN:

150510

Hom.:

1499

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.0759

Gnomad AMR

AF:

0.0781

Gnomad ASJ

AF:

0.0449

Gnomad EAS

AF:

0.000785

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.112

Gnomad NFE

AF:

0.0897

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.0761

AC:

AN:

368

Hom.:

AF XY:

0.0607

AC XY:

AN XY:

214

show subpopulations

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0795

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0893

AC:

90272

AN:

1010324

Hom.:

4228

Cov.:

AF XY:

0.0881

AC XY:

42418

AN XY:

481312

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.0657

Gnomad4 ASJ exome

AF:

0.0434

Gnomad4 EAS exome

AF:

0.000240

Gnomad4 SAS exome

AF:

0.0275

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.0907

Gnomad4 OTH exome

AF:

0.0824

GnomAD4 genome

AF:

0.123

AC:

18597

AN:

150622

Hom.:

1501

Cov.:

AF XY:

0.122

AC XY:

8973

AN XY:

73512

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.0779

Gnomad4 ASJ

AF:

0.0449

Gnomad4 EAS

AF:

0.000787

Gnomad4 SAS

AF:

0.0282

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.0896

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0991

Hom.:

119

TwinsUK

AF:

0.0876

AC:

325

ALSPAC

AF:

0.0934

AC:

360

ExAC

AF:

0.00742

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.25

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.53

REVEL

Benign

0.18

Sift

Benign

0.43

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.072

MPC

0.79

ClinPred

0.029

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.056

gMVP

0.51

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