chr7-129189194-C-G

Position:

• chr7-129189194-C-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_005631.5(SMO):​c.43C>G​(p.Leu15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMO NM_005631.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.567

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16650295).
• BP6: Variant 7-129189194-C-G is Benign according to our data. Variant chr7-129189194-C-G is described in ClinVar as [Benign]. Clinvar id is 2444000.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMO	NM_005631.5	c.43C>G	p.Leu15Val	missense_variant	1/12	ENST00000249373.8
SMO	XM_047420759.1	c.-462C>G		5_prime_UTR_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMO	ENST00000249373.8	c.43C>G	p.Leu15Val	missense_variant	1/12	1	NM_005631.5	P1
SMO	ENST00000655644.1	c.43C>G	p.Leu15Val	missense_variant, NMD_transcript_variant	1/12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 17

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

See cases Benign:1

Benign, no assertion criteria provided

clinical testing;research

Human Disease Genetics and Animal Model Lab, Shanxi University

Jul 31, 2022

The Leu15Val variant in SMO has been reported in1 Chinese female with spontenous abortion, and was absent from large population studies. Additionally, functional study indicate that the Leu15Val variant has no effect on SMO activity as this variant still can fully rescue the Hh activity loss of function in smo zebrafish mutant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.26
Sift	Benign	0.34	T
Sift4G	Benign	0.075	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.090		Loss of glycosylation at P13 (P = 0.2581);
MVP		0.50
MPC		0.61
ClinPred		0.13	T
GERP RS		3.2
Varity_R		0.097
gMVP		0.47

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: chr7-128829035;