rs34983516

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003276.2(TMPO):c.1805A>G(p.Gln602Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,609,278 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00089 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

TMPO
NM_003276.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.97

Publications

5 publications found

Variant links:

Genes affected

TMPO (HGNC:11875): (thymopoietin) Through alternative splicing, this gene encodes several distinct LEM domain containing protein isoforms. LEM domain proteins include inner nuclear membrane and intranuclear proteins, and are involved in a variety of cellular functions including gene expression, chromatin organization, and replication and cell cycle control. The encoded alpha isoform is broadly diffuse in the nucleus and contains a lamin binding domain, while the beta and gamma isoforms are localized to the nuclear membrane and contain an HDAC3 interaction domain. The distinct isoforms may compete with each other when acting to chaperone other proteins and regulate transcription. [provided by RefSeq, Aug 2019]

TMPO Gene-Disease associations (from GenCC):

familial isolated dilated cardiomyopathy
Inheritance: Unknown, AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet
hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
dilated cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

TMPO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004064113).

BP6

Variant 12-98534062-A-G is Benign according to our data. Variant chr12-98534062-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 178144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 135 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003276.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMPO	NM_001032283.3	MANE Select	c.565+2224A>G		intron	N/A	NP_001027454.1	P42167-1
TMPO	NM_003276.2		c.1805A>G	p.Gln602Arg	missense	Exon 4 of 4	NP_003267.1	P42166-1
TMPO	NM_001307975.2		c.565+2224A>G		intron	N/A	NP_001294904.1	G5E972

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMPO	ENST00000266732.8	TSL:1	c.1805A>G	p.Gln602Arg	missense	Exon 4 of 4	ENSP00000266732.4	P42166-1
TMPO	ENST00000556029.6	TSL:1 MANE Select	c.565+2224A>G		intron	N/A	ENSP00000450627.1	P42167-1
TMPO	ENST00000393053.6	TSL:1	c.565+2224A>G		intron	N/A	ENSP00000376773.2	P42167-2

Frequencies

GnomAD3 genomes

AF:

0.000874

AC:

133

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000236

AC:

AN:

250250

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000968

AC:

141

AN:

1456900

Hom.:

Cov.:

AF XY:

0.0000746

AC XY:

AN XY:

723520

show subpopulations

African (AFR)

AF:

0.00270

AC:

AN:

33394

American (AMR)

AF:

0.000112

AC:

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39552

South Asian (SAS)

AF:

0.00

AC:

AN:

86184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000271

AC:

AN:

1107848

Other (OTH)

AF:

0.000266

AC:

AN:

60106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000886

AC:

135

AN:

152378

Hom.:

Cov.:

AF XY:

0.000939

AC XY:

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.00286

AC:

119

AN:

41590

American (AMR)

AF:

0.000849

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000204

Hom.:

Bravo

AF:

0.000971

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000329

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Loeys-Dietz syndrome 2 (1)

not provided (1)

TMPO-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.10

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.42

M_CAP

Benign

0.0081

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

PhyloP100

2.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.38

REVEL

Benign

0.067

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.057

Polyphen

0.0030

Vest4

0.12

MVP

0.28

MPC

0.073

ClinPred

0.012

GERP RS

3.6

Varity_R

0.096

gMVP

0.037

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over