Variant 7-129203436-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_005631.5(SMO):c.384C>T(p.Ala128Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,565,174 control chromosomes in the GnomAD database, including 163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 12 hom., cov: 32)

Exomes 𝑓: 0.013 ( 151 hom. )

Consequence

SMO
NM_005631.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.63

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 7-129203436-C-T is Benign according to our data. Variant chr7-129203436-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1217539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.63 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00908 (1383/152304) while in subpopulation NFE AF= 0.0142 (964/68022). AF 95% confidence interval is 0.0134. There are 12 homozygotes in gnomad4. There are 609 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 SM gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMO	NM_005631.5 linkuse as main transcript	c.384C>T	p.Ala128Ala	synonymous_variant	2/12	ENST00000249373.8	NP_005622.1	Q99835
SMO	XM_047420759.1 linkuse as main transcript	c.-7C>T		5_prime_UTR_premature_start_codon_gain_variant	3/13		XP_047276715.1
SMO	XM_047420759.1 linkuse as main transcript	c.-7C>T		5_prime_UTR_variant	3/13		XP_047276715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMO	ENST00000249373.8 linkuse as main transcript	c.384C>T	p.Ala128Ala	synonymous_variant	2/12	1	NM_005631.5	ENSP00000249373.3	Q99835
SMO	ENST00000655644.1 linkuse as main transcript	n.*248C>T		non_coding_transcript_exon_variant	3/12			ENSP00000499377.1	A0A590UJE7
SMO	ENST00000655644.1 linkuse as main transcript	n.*248C>T		3_prime_UTR_variant	3/12			ENSP00000499377.1	A0A590UJE7

Frequencies

GnomAD3 genomes

AF:

0.00909

AC:

1383

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00207

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00941

AC:

1645

AN:

174906

Hom.:

AF XY:

0.00951

AC XY:

886

AN XY:

93196

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.00375

Gnomad ASJ exome

AF:

0.0214

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00824

Gnomad FIN exome

AF:

0.00888

Gnomad NFE exome

AF:

0.0133

Gnomad OTH exome

AF:

0.0123

GnomAD4 exome

AF:

0.0134

AC:

18880

AN:

1412870

Hom.:

151

Cov.:

AF XY:

0.0132

AC XY:

9209

AN XY:

698412

show subpopulations

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.00443

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00845

Gnomad4 FIN exome

AF:

0.0106

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.00908

AC:

1383

AN:

152304

Hom.:

Cov.:

AF XY:

0.00818

AC XY:

609

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.00582

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.0105

Gnomad4 NFE

AF:

0.0142

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.00877

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely 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	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	SMO: BP4, BP7, BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 15, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

2.0

DANN

Benign

0.85

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