7-129203555-G-T

Variant names:

• chr7-129203555-G-T
• NM_005631.5:c.503G>T

Variant summary

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

The NM_005631.5(SMO):​c.503G>T​(p.Arg168Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMO NM_005631.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.28

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMO	NM_005631.5	c.503G>T	p.Arg168Leu	missense_variant	Exon 2 of 12	ENST00000249373.8	NP_005622.1
SMO	XM_047420759.1	c.113G>T	p.Arg38Leu	missense_variant	Exon 3 of 13		XP_047276715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMO	ENST00000249373.8	c.503G>T	p.Arg168Leu	missense_variant	Exon 2 of 12	1	NM_005631.5	ENSP00000249373.3
SMO	ENST00000655644.1	n.*367G>T		non_coding_transcript_exon_variant	Exon 3 of 12			ENSP00000499377.1
SMO	ENST00000655644.1	n.*367G>T		3_prime_UTR_variant	Exon 3 of 12			ENSP00000499377.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1451604 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722268

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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	0.14
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.021	D
Polyphen		0.080	B
Vest4		0.56
MutPred		0.62		Loss of disorder (P = 0.0339);
MVP		0.83
MPC		1.4
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.48
gMVP		0.66

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: chr7-128843396; COSMIC: COSV50832064; COSMIC: COSV50832064;