chr8-132888141-T-C

Variant names:

Variant summary

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

The NM_003235.5(TG):c.2334T>C(p.Pro778Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,613,406 control chromosomes in the GnomAD database, including 241,744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28101 hom., cov: 31)

Exomes 𝑓: 0.54 ( 213643 hom. )

Consequence

TG
NM_003235.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -7.75

Variant links:

Genes affected

TG (HGNC:11764): (thyroglobulin) Thyroglobulin (Tg) is a glycoprotein homodimer produced predominantly by the thryroid gland. It acts as a substrate for the synthesis of thyroxine and triiodothyronine as well as the storage of the inactive forms of thyroid hormone and iodine. Thyroglobulin is secreted from the endoplasmic reticulum to its site of iodination, and subsequent thyroxine biosynthesis, in the follicular lumen. Mutations in this gene cause thyroid dyshormonogenesis, manifested as goiter, and are associated with moderate to severe congenital hypothyroidism. Polymorphisms in this gene are associated with susceptibility to autoimmune thyroid diseases (AITD) such as Graves disease and Hashimoto thryoiditis. [provided by RefSeq, Nov 2009]

TG 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=-1.0).

BP6

Variant 8-132888141-T-C is Benign according to our data. Variant chr8-132888141-T-C is described in ClinVar as [Benign]. Clinvar id is 258989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-132888141-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-7.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TG	NM_003235.5 link	c.2334T>C	p.Pro778Pro	synonymous_variant	Exon 10 of 48	ENST00000220616.9	NP_003226.4	P01266-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TG	ENST00000220616.9 link	c.2334T>C	p.Pro778Pro	synonymous_variant	Exon 10 of 48	1	NM_003235.5	ENSP00000220616.4		P01266-1

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91302

AN:

151814

Hom.:

28063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.708

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.596

Gnomad ASJ

AF:

0.617

Gnomad EAS

AF:

0.763

Gnomad SAS

AF:

0.661

Gnomad FIN

AF:

0.598

Gnomad MID

AF:

0.567

Gnomad NFE

AF:

0.522

Gnomad OTH

AF:

0.592

GnomAD3 exomes

AF:

0.581

AC:

145393

AN:

250364

Hom.:

42975

AF XY:

0.582

AC XY:

78715

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.712

Gnomad AMR exome

AF:

0.552

Gnomad ASJ exome

AF:

0.608

Gnomad EAS exome

AF:

0.763

Gnomad SAS exome

AF:

0.647

Gnomad FIN exome

AF:

0.582

Gnomad NFE exome

AF:

0.521

Gnomad OTH exome

AF:

0.576

GnomAD4 exome

AF:

0.536

AC:

783891

AN:

1461474

Hom.:

213643

Cov.:

AF XY:

0.540

AC XY:

392394

AN XY:

727018

show subpopulations

Gnomad4 AFR exome

AF:

0.712

Gnomad4 AMR exome

AF:

0.561

Gnomad4 ASJ exome

AF:

0.611

Gnomad4 EAS exome

AF:

0.761

Gnomad4 SAS exome

AF:

0.651

Gnomad4 FIN exome

AF:

0.579

Gnomad4 NFE exome

AF:

0.508

Gnomad4 OTH exome

AF:

0.560

GnomAD4 genome

AF:

0.602

AC:

91390

AN:

151932

Hom.:

28101

Cov.:

AF XY:

0.609

AC XY:

45189

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.708

Gnomad4 AMR

AF:

0.596

Gnomad4 ASJ

AF:

0.617

Gnomad4 EAS

AF:

0.764

Gnomad4 SAS

AF:

0.661

Gnomad4 FIN

AF:

0.598

Gnomad4 NFE

AF:

0.522

Gnomad4 OTH

AF:

0.584

Alfa

AF:

0.543

Hom.:

42175

Bravo

AF:

0.605

Asia WGS

AF:

0.678

AC:

2359

AN:

3478

EpiCase

AF:

0.535

EpiControl

AF:

0.535

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Iodotyrosyl coupling defect

Benign:2

Jan 13, 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. -

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0030

DANN

Benign

0.37

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