NM_001020658.2(PUM1):c.3439C>T (p.Arg1147Trp) AND Spinocerebellar ataxia 47

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 24, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000755727.8

Allele description [Variation Report for NM_001020658.2(PUM1):c.3439C>T (p.Arg1147Trp)]

NM_001020658.2(PUM1):c.3439C>T (p.Arg1147Trp)

Gene:

PUM1:pumilio RNA binding family member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p35.2

Genomic location:

Preferred name:

NM_001020658.2(PUM1):c.3439C>T (p.Arg1147Trp)

HGVS:

NC_000001.11:g.30933339G>A
NM_001020658.2:c.3439C>TMANE SELECT
NM_014676.3:c.3433C>T
NP_001018494.1:p.Arg1147Trp
NP_055491.1:p.Arg1145Trp
NC_000001.10:g.31406186G>A
NM_001020658.1:c.3439C>T

Protein change:

R1145W; ARG1147TRP

Links:

OMIM: 607204.0002; dbSNP: rs1557539450

NCBI 1000 Genomes Browser:

rs1557539450

Molecular consequence:

NM_001020658.2:c.3439C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_014676.3:c.3433C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

effect on RNA stability [Variation Ontology: 0301]

Observations:

Condition(s)

Name:: Spinocerebellar ataxia 47
Identifiers:: MONDO: MONDO:0033482; MedGen: C4693672; OMIM: 617931

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001439354	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-SouthSeq	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 24, 2020)	de novo	research	PubMed (1) [See all records that cite this PMID]
SCV001976645	Neurology Department, Shenzhen Children's Hospital	no assertion criteria provided	Pathogenic	de novo	clinical testing
SCV003804165	Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	de novo	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29474920, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001439354

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-SouthSeq

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 24, 2020)

de novo

research

PubMed (1)
[See all records that cite this PMID]

SCV001976645

Neurology Department, Shenzhen Children's Hospital

no assertion criteria provided

Pathogenic

de novo

clinical testing

SCV003804165

Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

de novo

clinical testing

PubMed (2)
[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	de novo	yes	2	not provided	not provided	1	not provided	clinical testing, research
Asian	de novo	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Mild PUM1 Mutation Is Associated with Adult-Onset Ataxia, whereas Haploinsufficiency Causes Developmental Delay and Seizures.

Gennarino VA, Palmer EE, McDonell LM, Wang L, Adamski CJ, Koire A, See L, Chen CA, Schaaf CP, Rosenfeld JA, Panzer JA, Moog U, Hao S, Bye A, Kirk EP, Stankiewicz P, Breman AM, McBride A, Kandula T, Dubbs HA, Macintosh R, Cardamone M, et al.

Cell. 2018 Feb 22;172(5):924-936.e11. doi: 10.1016/j.cell.2018.02.006.

PubMed [citation]

PMID:: 29474920
PMCID:: PMC5832058

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-SouthSeq, SCV001439354.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (1)

Description

ACMG codes:PS2; PS3; PS4M; PM2; PP3

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

From Neurology Department, Shenzhen Children's Hospital, SCV001976645.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Asian	1	not provided	not provided	clinical testing	not provided

Description

Trio-based WES revealed that the exon 22 of the PUM1 gene had a de novo heterozygous missense variant which is otherwise absent in population databases (dbSNP, ExAC, and GnomAD). Thus far, at least three unrelated patients with this variant have been reported (Bonnemason-Carrere et al., 2019; Gennarino et al., 2018; Voet et al., 2020), and all of them were de novo. Upon Western blotting analysis, it was found that the PUM1 protein stability was markedly compromised by this variant (Gennarino et al., 2018). Taken together, according to the American college of medical genetics and genomics guidelines, this variant is considered pathogenic (Richards et al., 2015).

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

From Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, SCV003804165.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	not provided	not provided	clinical testing	PubMed (2)

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

Last Updated: Nov 24, 2024

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