rs2739136

chr8-133056947-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003235.5(TG):c.7239+26924G>A 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 152,048 control chromosomes in the GnomAD database, including 43,771 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 (43771 hom., cov: 31)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

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]

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]

PTCSC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLA	NM_001045556.3	c.61+3153C>T		intron_variant		ENST00000338087.10
TG	NM_003235.5	c.7239+26924G>A		intron_variant		ENST00000220616.9
PTCSC1	NR_146773.1	n.1989G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TG	ENST00000220616.9	c.7239+26924G>A		intron_variant		1	NM_003235.5	P1
SLA	ENST00000338087.10	c.61+3153C>T		intron_variant		1	NM_001045556.3	P1
PTCSC1	ENST00000664551.1	n.1989G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113997 AN: 151930 Hom.: 43719 Cov.: 31

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.735

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: 114096 AN: 152048 Hom.: 43771 Cov.: 31 AF XY: 0.743 AC XY: 55206 AN XY: 74312

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.717

Alfa AF: 0.753 Hom.: 5393

Bravo AF: 0.747

Asia WGS AF: 0.515 AC: 1796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.1
Dann	Benign	0.39

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

Other links and lift over

dbSNP: rs2739136; hg19: chr8-134069192;