rs767503744

Variant names:

• chr14-69952153-C-G
• rs767503744
• NM_001034852.3:c.115C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-69952153-C-G
• chr14-69952153-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001034852.3(SMOC1):​c.115C>G​(p.Arg39Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R39C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SMOC1 NM_001034852.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 2 publications found

Genes affected

SMOC1 (HGNC:20318): (SPARC related modular calcium binding 1) This gene encodes a multi-domain secreted protein that may have a critical role in ocular and limb development. Mutations in this gene are associated with microphthalmia and limb anomalies. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

SMOC1 Gene-Disease associations (from GenCC):

• microphthalmia with limb anomalies

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034852.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	NM_001034852.3	MANE Select	c.115C>G	p.Arg39Gly	missense	Exon 2 of 12	NP_001030024.1	Q9H4F8-2
	SMOC1	NM_001425244.1		c.115C>G	p.Arg39Gly	missense	Exon 2 of 12	NP_001412173.1
	SMOC1	NM_001425245.1		c.115C>G	p.Arg39Gly	missense	Exon 2 of 12	NP_001412174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	ENST00000361956.8	TSL:1 MANE Select	c.115C>G	p.Arg39Gly	missense	Exon 2 of 12	ENSP00000355110.4	Q9H4F8-2
	SMOC1	ENST00000381280.4	TSL:1	c.115C>G	p.Arg39Gly	missense	Exon 2 of 12	ENSP00000370680.4	Q9H4F8-1
	SMOC1	ENST00000853906.1		c.115C>G	p.Arg39Gly	missense	Exon 2 of 13	ENSP00000523965.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000225 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	0.0030	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.18
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.62
MutPred		0.40		Loss of solvent accessibility (P = 0.1077)
MVP		0.73
MPC		1.1
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.54
gMVP		0.49
Mutation Taster		=30/70	disease causing

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: rs767503744; hg19: chr14-70418870;