rs143083812

chr7-129203569-C-Achr7-129203569-C-Gchr7-129203569-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005631.5(SMO):c.517C>A(p.Arg173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R173C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SMO NM_005631.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1741418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMO	NM_005631.5	c.517C>A	p.Arg173Ser	missense_variant	2/12	ENST00000249373.8
SMO	XM_047420759.1	c.127C>A	p.Arg43Ser	missense_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMO	ENST00000249373.8	c.517C>A	p.Arg173Ser	missense_variant	2/12	1	NM_005631.5	P1
SMO	ENST00000655644.1	c.*381C>A		3_prime_UTR_variant, NMD_transcript_variant	3/12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449608 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 721308

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.64	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.15
Sift	Benign	0.40	T
Sift4G	Benign	0.41	T
Polyphen		0.023	B
Vest4		0.29
MutPred		0.53		Gain of phosphorylation at R173 (P = 0.1459);
MVP		0.72
MPC		0.75
ClinPred		0.68	D
GERP RS		3.5
Varity_R		0.22
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-128843410; COSMIC: COSV50829401; COSMIC: COSV50829401;