NM_001034852.3(SMOC1):c.274C>T (p.Gln92Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 25, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003557825.2

Allele description [Variation Report for NM_001034852.3(SMOC1):c.274C>T (p.Gln92Ter)]

NM_001034852.3(SMOC1):c.274C>T (p.Gln92Ter)

Gene:

SMOC1:SPARC related modular calcium binding 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q24.2

Genomic location:

Preferred name:

NM_001034852.3(SMOC1):c.274C>T (p.Gln92Ter)

HGVS:

NC_000014.9:g.69953428C>T
NG_028217.1:g.79032C>T
NG_129390.1:g.449C>T
NM_001034852.3:c.274C>TMANE SELECT
NM_001425244.1:c.274C>T
NM_001425245.1:c.274C>T
NM_022137.6:c.274C>T
NP_001030024.1:p.Gln92Ter
NP_001412173.1:p.Gln92Ter
NP_001412174.1:p.Gln92Ter
NP_071420.1:p.Gln92Ter
NC_000014.8:g.70420145C>T

Protein change:

Q92*

Molecular consequence:

NM_001034852.3:c.274C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001425244.1:c.274C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001425245.1:c.274C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_022137.6:c.274C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004297118	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 25, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21194678, 21750680, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004297118

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 25, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

SMOC1 is essential for ocular and limb development in humans and mice.

Okada I, Hamanoue H, Terada K, Tohma T, Megarbane A, Chouery E, Abou-Ghoch J, Jalkh N, Cogulu O, Ozkinay F, Horie K, Takeda J, Furuichi T, Ikegawa S, Nishiyama K, Miyatake S, Nishimura A, Mizuguchi T, Niikawa N, Hirahara F, Kaname T, Yoshiura K, et al.

Am J Hum Genet. 2011 Jan 7;88(1):30-41. doi: 10.1016/j.ajhg.2010.11.012. Epub 2010 Dec 30.

PubMed [citation]

PMID:: 21194678
PMCID:: PMC3014372

Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice.

Rainger J, van Beusekom E, Ramsay JK, McKie L, Al-Gazali L, Pallotta R, Saponari A, Branney P, Fisher M, Morrison H, Bicknell L, Gautier P, Perry P, Sokhi K, Sexton D, Bardakjian TM, Schneider AS, Elcioglu N, Ozkinay F, Koenig R, Mégarbané A, Semerci CN, et al.

PLoS Genet. 2011 Jul;7(7):e1002114. doi: 10.1371/journal.pgen.1002114. Epub 2011 Jul 7. Erratum in: PLoS Genet. 2018 Dec 26;14(12):e1007866. doi: 10.1371/journal.pgen.1007866.

PubMed [citation]

PMID:: 21750680
PMCID:: PMC3131273

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297118.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln92*) in the SMOC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMOC1 are known to be pathogenic (PMID: 21194678). This variant is present in population databases (rs781216969, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with ophthalmo-acromelic syndrome (PMID: 21750680). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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