Genetic Variant TG:c.7239+18792G>T (chr8-133048815-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003235.5(TG):c.7239+18792G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000571 in 17,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

TG
NM_003235.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.605

Publications

1 publications found

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:

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003235.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TG	NM_003235.5	MANE Select	c.7239+18792G>T	intron	N/A	NP_003226.4
SLA	NM_001045556.3	MANE Select	c.249-882C>A	intron	N/A	NP_001039021.1
SLA	NM_006748.4		c.369-882C>A	intron	N/A	NP_006739.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TG	ENST00000220616.9	TSL:1 MANE Select	c.7239+18792G>T	intron	N/A	ENSP00000220616.4
SLA	ENST00000338087.10	TSL:1 MANE Select	c.249-882C>A	intron	N/A	ENSP00000337548.5
SLA	ENST00000427060.6	TSL:1	c.369-882C>A	intron	N/A	ENSP00000394049.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000571

AC:

AN:

17516

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

9390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

546

American (AMR)

AF:

0.00

AC:

AN:

1856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

388

East Asian (EAS)

AF:

0.00

AC:

AN:

948

South Asian (SAS)

AF:

0.00

AC:

AN:

2846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000106

AC:

AN:

9434

Other (OTH)

AF:

0.00

AC:

AN:

768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.13

(source)

DANN

Benign

0.49

PhyloP100

-0.60

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over