NM_002087.4(GRN):c.348A>C (p.Ser116=) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 3, 2023
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:: RCV003783717.1

Allele description [Variation Report for NM_002087.4(GRN):c.348A>C (p.Ser116=)]

NM_002087.4(GRN):c.348A>C (p.Ser116=)

Gene:

GRN:granulin precursor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_002087.4(GRN):c.348A>C (p.Ser116=)

HGVS:

NC_000017.11:g.44349750A>C
NG_007886.1:g.9628A>C
NM_002087.4:c.348A>CMANE SELECT
NP_002078.1:p.Ser116=
NP_002078.1:p.Ser116=
LRG_661t1:c.348A>C
LRG_661:g.9628A>C
LRG_661p1:p.Ser116=
NC_000017.10:g.42427118A>C
NM_002087.2:c.348A>C

Molecular consequence:

NM_002087.4:c.348A>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: GRN-related frontotemporal lobar degeneration with Tdp43 inclusions
Synonyms:: FRONTOTEMPORAL LOBAR DEGENERATION WITH UBIQUITIN-POSITIVE INCLUSIONS; FTLD-TDP, GRN-RELATED; Frontotemporal dementia, ubiquitin-positive; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011842; MedGen: C1843792; Orphanet: 100070; Orphanet: 282; OMIM: 607485

Name:: Neuronal ceroid lipofuscinosis 11
Synonyms:: GRN-Related Neuronal Ceroid-Lipofuscinosis
Identifiers:: MONDO: MONDO:0013866; MedGen: C3539123; Orphanet: 314629; Orphanet: 79262; OMIM: 614706

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004571435	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 3, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20142524, 21482928, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004571435

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 3, 2023)

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

The spectrum of mutations in progranulin: a collaborative study screening 545 cases of neurodegeneration.

Yu CE, Bird TD, Bekris LM, Montine TJ, Leverenz JB, Steinbart E, Galloway NM, Feldman H, Woltjer R, Miller CA, Wood EM, Grossman M, McCluskey L, Clark CM, Neumann M, Danek A, Galasko DR, Arnold SE, Chen-Plotkin A, Karydas A, Miller BL, Trojanowski JQ, et al.

Arch Neurol. 2010 Feb;67(2):161-70. doi: 10.1001/archneurol.2009.328.

PubMed [citation]

PMID:: 20142524
PMCID:: PMC2901991

Genetic and clinical features of progranulin-associated frontotemporal lobar degeneration.

Chen-Plotkin AS, Martinez-Lage M, Sleiman PM, Hu W, Greene R, Wood EM, Bing S, Grossman M, Schellenberg GD, Hatanpaa KJ, Weiner MF, White CL 3rd, Brooks WS, Halliday GM, Kril JJ, Gearing M, Beach TG, Graff-Radford NR, Dickson DW, Rademakers R, Boeve BF, Pickering-Brown SM, et al.

Arch Neurol. 2011 Apr;68(4):488-97. doi: 10.1001/archneurol.2011.53.

PubMed [citation]

PMID:: 21482928
PMCID:: PMC3160280

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004571435.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has been observed in individual(s) with frontotemporal lobar degeneration (PMID: 20142524, 21482928). This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 116 of the GRN mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GRN protein. It affects a nucleotide within the consensus splice site.

#	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: Mar 5, 2024

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