NM_001206744.2:c.2145C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001206744.2(TPO):c.2145C>T(p.Pro715Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,612,706 control chromosomes in the GnomAD database, including 136,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13520 hom., cov: 33)

Exomes 𝑓: 0.41 ( 122590 hom. )

Consequence

TPO
NM_001206744.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.72

Variant links:

Genes affected

TPO (HGNC:12015): (thyroid peroxidase) This gene encodes a membrane-bound glycoprotein. The encoded protein acts as an enzyme and plays a central role in thyroid gland function. The protein functions in the iodination of tyrosine residues in thyroglobulin and phenoxy-ester formation between pairs of iodinated tyrosines to generate the thyroid hormones, thyroxine and triiodothyronine. Mutations in this gene are associated with several disorders of thyroid hormonogenesis, including congenital hypothyroidism, congenital goiter, and thyroid hormone organification defect IIA. Multiple transcript variants encoding distinct isoforms have been identified for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, May 2011]

TPO links:

ENSG00000231482 (HGNC:):

ENSG00000231482 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 2-1496127-C-T is Benign according to our data. Variant chr2-1496127-C-T is described in ClinVar as [Benign]. Clinvar id is 256610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-1496127-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.72 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPO	NM_001206744.2 link	c.2145C>T	p.Pro715Pro	synonymous_variant	Exon 12 of 17	ENST00000329066.9	NP_001193673.1	P07202-1Q502Y3Q6P534

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPO	ENST00000329066.9 link	c.2145C>T	p.Pro715Pro	synonymous_variant	Exon 12 of 17	1	NM_001206744.2	ENSP00000329869.4		P07202-1

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63965

AN:

151950

Hom.:

13505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.418

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.420

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.426

GnomAD3 exomes

AF:

0.415

AC:

103605

AN:

249478

Hom.:

21758

AF XY:

0.416

AC XY:

56127

AN XY:

134822

show subpopulations

Gnomad AFR exome

AF:

0.435

Gnomad AMR exome

AF:

0.437

Gnomad ASJ exome

AF:

0.364

Gnomad EAS exome

AF:

0.410

Gnomad SAS exome

AF:

0.506

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.388

Gnomad OTH exome

AF:

0.404

GnomAD4 exome

AF:

0.408

AC:

595673

AN:

1460638

Hom.:

122590

Cov.:

AF XY:

0.410

AC XY:

297931

AN XY:

726516

show subpopulations

Gnomad4 AFR exome

AF:

0.450

Gnomad4 AMR exome

AF:

0.439

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.451

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.412

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.416

GnomAD4 genome

AF:

0.421

AC:

64026

AN:

152068

Hom.:

13520

Cov.:

AF XY:

0.424

AC XY:

31487

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.443

Gnomad4 AMR

AF:

0.458

Gnomad4 ASJ

AF:

0.374

Gnomad4 EAS

AF:

0.418

Gnomad4 SAS

AF:

0.497

Gnomad4 FIN

AF:

0.420

Gnomad4 NFE

AF:

0.397

Gnomad4 OTH

AF:

0.424

Alfa

AF:

0.384

Hom.:

6912

Bravo

AF:

0.420

Asia WGS

AF:

0.457

AC:

1589

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Deficiency of iodide peroxidase

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.4

DANN

Benign

0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over