rs146200641

Positions:

• chr7-129211755-C-A
• chr7-129211755-C-G
• chr7-129211755-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005631.5(SMO):​c.1921C>A​(p.Pro641Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. P641A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMO NM_005631.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.40

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMO	NM_005631.5	c.1921C>A	p.Pro641Thr	missense_variant	11/12	ENST00000249373.8
SMO	XM_047420759.1	c.1531C>A	p.Pro511Thr	missense_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMO	ENST00000249373.8	c.1921C>A	p.Pro641Thr	missense_variant	11/12	1	NM_005631.5	P1
	ENST00000466717.1	n.130-1575G>T		intron_variant, non_coding_transcript_variant		3
SMO	ENST00000475779.1	c.*225C>A		3_prime_UTR_variant, NMD_transcript_variant	4/5	3
SMO	ENST00000655644.1	c.*1676C>A		3_prime_UTR_variant, NMD_transcript_variant	11/12

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	0.18
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.67	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.59
Sift	Uncertain	0.013	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.40		Gain of glycosylation at P641 (P = 0.0225);
MVP		0.93
MPC		0.36
ClinPred		0.92	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.46

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: chr7-128851596;