14-69952153-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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]

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
SMOC1	NM_001034852.3	c.115C>G	p.Arg39Gly	missense_variant	Exon 2 of 12	ENST00000361956.8	NP_001030024.1
SMOC1	NM_001425244.1	c.115C>G	p.Arg39Gly	missense_variant	Exon 2 of 12		NP_001412173.1
SMOC1	NM_001425245.1	c.115C>G	p.Arg39Gly	missense_variant	Exon 2 of 12		NP_001412174.1
SMOC1	NM_022137.6	c.115C>G	p.Arg39Gly	missense_variant	Exon 2 of 12		NP_071420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8	c.115C>G	p.Arg39Gly	missense_variant	Exon 2 of 12	1	NM_001034852.3	ENSP00000355110.4
SMOC1	ENST00000381280.4	c.115C>G	p.Arg39Gly	missense_variant	Exon 2 of 12	1		ENSP00000370680.4
SMOC1	ENST00000553839.1	n.17C>G		non_coding_transcript_exon_variant	Exon 1 of 4	5
SMOC1	ENST00000555917.1	n.420C>G		non_coding_transcript_exon_variant	Exon 4 of 4	4

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

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000225 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.18
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.99	D;P
Vest4		0.62
MutPred		0.40		Loss of solvent accessibility (P = 0.1077);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

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

LitVar

Other links and lift over

dbSNP: rs767503744; hg19: chr14-70418870;