Variant 8-133094979-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003235.5(TG):c.7240-65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,608,604 control chromosomes in the GnomAD database, including 422,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.73 ( 41302 hom., cov: 32)

Exomes 𝑓: 0.72 ( 381438 hom. )

Consequence

TG
NM_003235.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.344

Variant links:

Genes affected

SLA (HGNC:10902): (Src like adaptor) Predicted to enable signaling receptor binding activity. Predicted to be involved in cell differentiation; innate immune response; and transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to be located in cytosol. Predicted to be active in dendritic spine and focal adhesion. Predicted to be extrinsic component of cytoplasmic side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLA links:

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 8-133094979-A-G is Benign according to our data. Variant chr8-133094979-A-G is described in ClinVar as [Benign]. Clinvar id is 1283196.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLA	NM_001045556.3 linkuse as main transcript	c.-319+7574T>C		intron_variant		ENST00000338087.10
TG	NM_003235.5 linkuse as main transcript	c.7240-65A>G		intron_variant		ENST00000220616.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TG	ENST00000220616.9 linkuse as main transcript	c.7240-65A>G		intron_variant		1	NM_003235.5	P1	P01266-1
SLA	ENST00000338087.10 linkuse as main transcript	c.-319+7574T>C		intron_variant		1	NM_001045556.3	P1	Q13239-1

Frequencies

GnomAD3 genomes

AF:

0.732

AC:

111272

AN:

151916

Hom.:

41268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.805

Gnomad AMI

AF:

0.700

Gnomad AMR

AF:

0.647

Gnomad ASJ

AF:

0.793

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.580

Gnomad FIN

AF:

0.704

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.739

GnomAD4 exome

AF:

0.719

AC:

1047698

AN:

1456570

Hom.:

381438

Cov.:

AF XY:

0.716

AC XY:

518980

AN XY:

724842

show subpopulations

Gnomad4 AFR exome

AF:

0.814

Gnomad4 AMR exome

AF:

0.580

Gnomad4 ASJ exome

AF:

0.798

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.591

Gnomad4 FIN exome

AF:

0.705

Gnomad4 NFE exome

AF:

0.743

Gnomad4 OTH exome

AF:

0.720

GnomAD4 genome

AF:

0.732

AC:

111349

AN:

152034

Hom.:

41302

Cov.:

AF XY:

0.725

AC XY:

53838

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.805

Gnomad4 AMR

AF:

0.647

Gnomad4 ASJ

AF:

0.793

Gnomad4 EAS

AF:

0.427

Gnomad4 SAS

AF:

0.582

Gnomad4 FIN

AF:

0.704

Gnomad4 NFE

AF:

0.743

Gnomad4 OTH

AF:

0.732

Alfa

AF:

0.740

Hom.:

31163

Bravo

AF:

0.728

Asia WGS

AF:

0.490

AC:

1709

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.74

DANN

Benign

0.43

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