8-133055287-G-C

Variant names:

• chr8-133055287-G-C
• rs2702969
• NM_003235.5:c.7239+25264G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003235.5(TG):​c.7239+25264G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 151,322 control chromosomes in the GnomAD database, including 43,510 homozygotes. 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: 𝑓 0.75 (43510 hom., cov: 27)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 3 publications found

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]

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]

PTCSC1 (HGNC:37127): (papillary thyroid carcinoma susceptibility candidate 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TG	NM_003235.5	MANE Select	c.7239+25264G>C		intron	N/A	NP_003226.4
	SLA	NM_001045556.3	MANE Select	c.62-4372C>G		intron	N/A	NP_001039021.1	Q13239-1
	SLA	NM_006748.4		c.182-4372C>G		intron	N/A	NP_006739.2	Q13239-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TG	ENST00000220616.9	TSL:1 MANE Select	c.7239+25264G>C		intron	N/A	ENSP00000220616.4	P01266-1
	SLA	ENST00000338087.10	TSL:1 MANE Select	c.62-4372C>G		intron	N/A	ENSP00000337548.5	Q13239-1
	SLA	ENST00000427060.6	TSL:1	c.182-4372C>G		intron	N/A	ENSP00000394049.2	Q13239-5

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113390 AN: 151204 Hom.: 43458 Cov.: 27

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.723

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.750 AC: 113489 AN: 151322 Hom.: 43510 Cov.: 27 AF XY: 0.742 AC XY: 54811 AN XY: 73820

African (AFR) AF: 0.890 AC: 36679 AN: 41212

American (AMR) AF: 0.629 AC: 9565 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2556 AN: 3466

East Asian (EAS) AF: 0.438 AC: 2246 AN: 5124

South Asian (SAS) AF: 0.578 AC: 2764 AN: 4784

European-Finnish (FIN) AF: 0.726 AC: 7530 AN: 10378

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.734 AC: 49805 AN: 67874

Other (OTH) AF: 0.717 AC: 1495 AN: 2086

Alfa AF: 0.690 Hom.: 2317

Bravo AF: 0.747

Asia WGS AF: 0.514 AC: 1790 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.68
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2702969; hg19: chr8-134067532;