NM_001134363.3(RBM20):c.448G>A (p.Ala150Thr) AND not specified

This record was updated by the submitter. Please see the current version.

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Jan 16, 2018
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:: RCV000036993.5

Allele description

NM_001134363.3(RBM20):c.448G>A (p.Ala150Thr)

Gene:

RBM20:RNA binding motif protein 20 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q25.2

Genomic location:

Preferred name:

NM_001134363.3(RBM20):c.448G>A (p.Ala150Thr)

Other names:

p.A150T:GCT>ACT

HGVS:

NC_000010.11:g.110781057G>A
NG_021177.1:g.141661G>A
NM_001134363.3:c.448G>AMANE SELECT
NP_001127835.2:p.Ala150Thr
LRG_382t1:c.448G>A
LRG_382:g.141661G>A
NC_000010.10:g.112540815G>A
NM_001134363.1:c.448G>A
NM_001134363.2:c.448G>A
c.448G>A

Protein change:

A150T

Links:

dbSNP: rs199868951

NCBI 1000 Genomes Browser:

rs199868951

Molecular consequence:

NM_001134363.3:c.448G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000060649	Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Dec 11, 2012)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000236303	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Jan 16, 2018)	germline	clinical testing	Citation Link,
SCV000280435	Stanford Center for Inherited Cardiovascular Disease, Stanford University	no assertion criteria provided	Uncertain significance (Jan 26, 2013)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000060649

Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely benign
(Dec 11, 2012)

germline

clinical testing

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

SCV000236303

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Benign
(Jan 16, 2018)

germline

clinical testing

Citation Link,

SCV000280435

Stanford Center for Inherited Cardiovascular Disease, Stanford University

no assertion criteria provided

Uncertain significance
(Jan 26, 2013)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	6	4	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000060649.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (1)

Description

Ala150Thr in exon 2 of RBM20: This variant is not expected to have clinical sign ificance due to a lack of conservation across species, including mammals. Of not e, 14 mammals have a Threonine (Thr; this variant) at this position despite high nearby amino acid conservation. In addition, computational analyses (AlignGVGD, PolyPhen2, SIFT) do not suggest a high likelihood of impact to the protein. In addition, this variant has been identified in 3/3182 European American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		5	not provided	4	not provided

From GeneDx, SCV000236303.12

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Stanford Center for Inherited Cardiovascular Disease, Stanford University, SCV000280435.1

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

Description

Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Ala150Thr (c.448 G>A, A150T) in the RBM20 gene The variant has not been reported in association with disease. In silico analysis with PolyPhen-2 predicts the variant to be benign. The alanine at codon 150 is not conserved across species, and is in fact a threonine in some species, including mammals. Mutation taster predicts the variant to be benign. In total the variant has not been seen in 5 of ~2,579 published controls and individuals from publicly available population datasets. The variant is reported online in 3 of 1591 Caucasian individuals and 1 of 692 African-American individuals in the NHLBI Exome Sequencing Project dataset (as of January 27th, 2013). The phenotype of those individuals is not publicly available, however the cohorts that were merged to create this dataset were all either general population samples or samples recruited for common cardiovascular disease such as hypertension. The variant is listed in dbSNP (rs199868951), which refers to the NHLBI data and data from ClinSeq. In ClinSeq it was observed in 1 of 296 individuals; this cohort approximates a general population sample (with respect to Mendelian disease). It is listed in 1000 genomes but only in reference to the dbSNP entry (as of January 27th, 2013).

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

Last Updated: Apr 8, 2022

ClinVar

Relating variation to medicine