NM_005631.5:c.*561C>G

Variant names:

• chr7-129213012-C-G
• rs3824
• NM_005631.5:c.*561C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005631.5(SMO):​c.*561C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 261,698 control chromosomes in the GnomAD database, including 2,803 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1580 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1223 hom.)
• Consequence: SMO NM_005631.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• Curry-Jones syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P
• congenital hypothalamic hamartoma syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, ClinGen
• Hirschsprung disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• medulloblastoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000243230 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMO	NM_005631.5	c.*561C>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000249373.8	NP_005622.1
SMO	XM_047420759.1	c.*561C>G		3_prime_UTR_variant	Exon 13 of 13		XP_047276715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMO	ENST00000249373.8	c.*561C>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_005631.5	ENSP00000249373.3
SMO	ENST00000655644.1	n.*2680C>G		non_coding_transcript_exon_variant	Exon 12 of 12			ENSP00000499377.1
SMO	ENST00000655644.1	n.*2680C>G		3_prime_UTR_variant	Exon 12 of 12			ENSP00000499377.1
ENSG00000243230	ENST00000466717.1	n.129+405G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21246 AN: 152076 Hom.: 1570 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.139 AC: 15267 AN: 109504 Hom.: 1223 Cov.: 0 AF XY: 0.138 AC XY: 7219 AN XY: 52198

African (AFR) AF: 0.138 AC: 615 AN: 4452

American (AMR) AF: 0.154 AC: 565 AN: 3660

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 613 AN: 5786

East Asian (EAS) AF: 0.248 AC: 3356 AN: 13522

South Asian (SAS) AF: 0.227 AC: 247 AN: 1086

European-Finnish (FIN) AF: 0.139 AC: 461 AN: 3312

Middle Eastern (MID) AF: 0.102 AC: 63 AN: 618

European-Non Finnish (NFE) AF: 0.120 AC: 8286 AN: 68912

Other (OTH) AF: 0.130 AC: 1061 AN: 8156

GnomAD4 genome AF: 0.140 AC: 21282 AN: 152194 Hom.: 1580 Cov.: 32 AF XY: 0.144 AC XY: 10696 AN XY: 74414

African (AFR) AF: 0.136 AC: 5656 AN: 41516

American (AMR) AF: 0.179 AC: 2731 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3470

East Asian (EAS) AF: 0.250 AC: 1293 AN: 5178

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4826

European-Finnish (FIN) AF: 0.131 AC: 1392 AN: 10602

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8391 AN: 68004

Other (OTH) AF: 0.137 AC: 289 AN: 2112

Alfa AF: 0.0502 Hom.: 51

Bravo AF: 0.140

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.39
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3824; hg19: chr7-128852853;