NM_001032283.3(TMPO):c.565+1782G>A AND not specified

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Nov 9, 2021
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:: RCV001293596.2

Allele description [Variation Report for NM_001032283.3(TMPO):c.565+1782G>A]

NM_001032283.3(TMPO):c.565+1782G>A

Gene:

TMPO:thymopoietin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q23.1

Genomic location:

Preferred name:

NM_001032283.3(TMPO):c.565+1782G>A

HGVS:

NC_000012.12:g.98533620G>A
NG_021393.1:g.23048G>A
NM_001032283.3:c.565+1782G>AMANE SELECT
NM_001032284.3:c.565+1782G>A
NM_001307975.2:c.565+1782G>A
NM_003276.2:c.1363G>A
NP_003267.1:p.Glu455Lys
LRG_443t2:c.1363G>A
LRG_443:g.23048G>A
LRG_443p2:p.Glu455Lys
NC_000012.11:g.98927398G>A

Protein change:

E455K

Links:

dbSNP: rs763388598

NCBI 1000 Genomes Browser:

rs763388598

Molecular consequence:

NM_001032283.3:c.565+1782G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001032284.3:c.565+1782G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001307975.2:c.565+1782G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_003276.2:c.1363G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001482213	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Feb 1, 2021)	germline	clinical testing	Citation Link,
SCV003572210	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Nov 9, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001482213

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(Feb 1, 2021)

germline

clinical testing

Citation Link,

SCV003572210

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Nov 9, 2021)

germline

clinical testing

Citation Link

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001482213.1

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

Description

Variant summary: TMPO c.1363G>A (p.Glu455Lys) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 251418 control chromosomes (gnomAD). The observed variant frequency is approximately 10-fold of the estimated maximal expected allele frequency for a pathogenic variant in TMPO causing Dilated Cardiomyopathy phenotype (1.6e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1363G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign.

#	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

From Ambry Genetics, SCV003572210.2

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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: Feb 25, 2025

ClinVar

Relating variation to medicine