8-133131869-C-T

Position:

chr8-133131869-C-T

Variant summary

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

The NM_003235.5(TG):c.7920C>T(p.Tyr2640=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,613,812 control chromosomes in the GnomAD database, including 180,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18754 hom., cov: 32)

Exomes 𝑓: 0.46 ( 161925 hom. )

Consequence

TG
NM_003235.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.250

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=-0.69).

BP6

Variant 8-133131869-C-T is Benign according to our data. Variant chr8-133131869-C-T is described in ClinVar as [Benign]. Clinvar id is 259003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-133131869-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TG	NM_003235.5 linkuse as main transcript	c.7920C>T	p.Tyr2640=	synonymous_variant	46/48	ENST00000220616.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TG	ENST00000220616.9 linkuse as main transcript	c.7920C>T	p.Tyr2640=	synonymous_variant	46/48	1	NM_003235.5	P1	P01266-1

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73948

AN:

151878

Hom.:

18735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.583

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.567

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.508

GnomAD3 exomes

AF:

0.428

AC:

107635

AN:

251420

Hom.:

24558

AF XY:

0.425

AC XY:

57743

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.586

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.313

Gnomad FIN exome

AF:

0.385

Gnomad NFE exome

AF:

0.487

Gnomad OTH exome

AF:

0.458

GnomAD4 exome

AF:

0.464

AC:

677945

AN:

1461816

Hom.:

161925

Cov.:

AF XY:

0.460

AC XY:

334335

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.591

Gnomad4 AMR exome

AF:

0.401

Gnomad4 ASJ exome

AF:

0.555

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.321

Gnomad4 FIN exome

AF:

0.394

Gnomad4 NFE exome

AF:

0.486

Gnomad4 OTH exome

AF:

0.471

GnomAD4 genome

AF:

0.487

AC:

73999

AN:

151996

Hom.:

18754

Cov.:

AF XY:

0.475

AC XY:

35323

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.583

Gnomad4 AMR

AF:

0.451

Gnomad4 ASJ

AF:

0.567

Gnomad4 EAS

AF:

0.164

Gnomad4 SAS

AF:

0.309

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.487

Gnomad4 OTH

AF:

0.503

Alfa

AF:

0.490

Hom.:

23598

Bravo

AF:

0.497

Asia WGS

AF:

0.239

AC:

830

AN:

3476

EpiCase

AF:

0.489

EpiControl

AF:

0.489

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 26, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Iodotyrosyl coupling defect

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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 specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.6

DANN

Benign

0.47

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