chr14-69879696-C-G

Position:

• chr14-69879696-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001034852.3(SMOC1):​c.18C>G​(p.Cys6Trp) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMOC1 NM_001034852.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17943081).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMOC1	NM_001034852.3	c.18C>G	p.Cys6Trp	missense_variant	1/12	ENST00000361956.8	NP_001030024.1
SMOC1	NM_022137.6	c.18C>G	p.Cys6Trp	missense_variant	1/12		NP_071420.1
SMOC1	XM_005267995.2	c.18C>G	p.Cys6Trp	missense_variant	1/12
SMOC1	XM_005267996.2	c.18C>G	p.Cys6Trp	missense_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8	c.18C>G	p.Cys6Trp	missense_variant	1/12	1	NM_001034852.3	ENSP00000355110.4
SMOC1	ENST00000381280.4	c.18C>G	p.Cys6Trp	missense_variant	1/12	1		ENSP00000370680.4
SMOC1	ENST00000555917.1	n.404+15482C>G		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

The c.18C>G (p.C6W) alteration is located in exon 1 (coding exon 1) of the SMOC1 gene. This alteration results from a C to G substitution at nucleotide position 18, causing the cysteine (C) at amino acid position 6 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Benign	0.83
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.67	T;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.12
Sift	Benign	0.050	D;D
Sift4G	Benign	0.19	T;T
Polyphen		0.0	B;B
Vest4		0.17
MutPred		0.53		Gain of MoRF binding (P = 4e-04);Gain of MoRF binding (P = 4e-04);
MVP		0.40
MPC		0.40
ClinPred		0.16	T
GERP RS		3.0
Varity_R		0.22
gMVP		0.47

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: chr14-70346413;