rs2228617

Variant names:

• chr7-129206487-G-A
• rs2228617
• NM_005631.5:c.1164G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-129206487-G-A
• chr7-129206487-G-C
• chr7-129206487-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005631.5(SMO):​c.1164G>A​(p.Gly388Gly) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G388G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SMO NM_005631.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 33 publications found

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]

SMO Gene-Disease associations (from GenCC):

• Curry-Jones syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P
• congenital hypothalamic hamartoma syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, ClinGen
• Hirschsprung disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• medulloblastoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMO	NM_005631.5	c.1164G>A	p.Gly388Gly	synonymous_variant	Exon 6 of 12	ENST00000249373.8	NP_005622.1
SMO	XM_047420759.1	c.774G>A	p.Gly258Gly	synonymous_variant	Exon 7 of 13		XP_047276715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMO	ENST00000249373.8	c.1164G>A	p.Gly388Gly	synonymous_variant	Exon 6 of 12	1	NM_005631.5	ENSP00000249373.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.8
DANN	Benign	0.89
PhyloP100		1.2

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

Other links and lift over

dbSNP: rs2228617; hg19: chr7-128846328;