Variant 7-129189250-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_005631.5(SMO):c.99C>A(p.Ser33Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,223,170 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

SMO
NM_005631.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.844

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000257 (275/1071520) while in subpopulation NFE AF= 0.000283 (258/910416). AF 95% confidence interval is 0.000255. There are 0 homozygotes in gnomad4_exome. There are 121 alleles in male gnomad4_exome subpopulation. Median coverage is 20. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMO	NM_005631.5 linkuse as main transcript	c.99C>A	p.Ser33Arg	missense_variant	1/12	ENST00000249373.8	NP_005622.1
SMO	XM_047420759.1 linkuse as main transcript	c.-406C>A		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.99C>A	p.Ser33Arg	missense_variant	1/12	1	NM_005631.5	ENSP00000249373	P1
SMO	ENST00000655644.1 linkuse as main transcript	c.99C>A	p.Ser33Arg	missense_variant, NMD_transcript_variant	1/12			ENSP00000499377

Frequencies

GnomAD3 genomes

AF:

0.0000857

AC:

AN:

151650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000192

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000257

AC:

275

AN:

1071520

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

121

AN XY:

510144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000283

Gnomad4 OTH exome

AF:

0.000394

GnomAD4 genome

AF:

0.0000857

AC:

AN:

151650

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74056

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000192

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

0.0066

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Benign

-0.029

Eigen_PC

Benign

-0.046

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.96

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.40

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.69

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.39

Sift

Uncertain

0.0040

Sift4G

Benign

0.30

Polyphen

0.99

Vest4

0.20

MutPred

0.27

Loss of glycosylation at S33 (P = 0.0034);

MVP

0.76

MPC

1.1

ClinPred

0.91

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.33

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over