7-129212144-C-A

Position:

• chr7-129212144-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005631.5(SMO):​c.2057C>A​(p.Ala686Glu) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMO NM_005631.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02696371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMO	NM_005631.5	c.2057C>A	p.Ala686Glu	missense_variant	12/12	ENST00000249373.8	NP_005622.1
SMO	XM_047420759.1	c.1667C>A	p.Ala556Glu	missense_variant	13/13		XP_047276715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMO	ENST00000249373.8	c.2057C>A	p.Ala686Glu	missense_variant	12/12	1	NM_005631.5	ENSP00000249373	P1
	ENST00000466717.1	n.129+1273G>T		intron_variant, non_coding_transcript_variant		3
SMO	ENST00000475779.1	c.*361C>A		3_prime_UTR_variant, NMD_transcript_variant	5/5	3		ENSP00000420749
SMO	ENST00000655644.1	c.*1812C>A		3_prime_UTR_variant, NMD_transcript_variant	12/12			ENSP00000499377

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.012
DANN	Benign	0.44
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.044
MutPred		0.082		Loss of MoRF binding (P = 0.0808);
MVP		0.23
MPC		0.077
ClinPred		0.031	T
GERP RS		-6.8
Varity_R		0.028
gMVP		0.20

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: chr7-128851985;