rs2702968

Positions:

• chr8-133056124-A-T

Variant summary

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

The NM_003235.5(TG):​c.7239+26101A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,996 control chromosomes in the GnomAD database, including 21,273 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 0.53 (21273 hom., cov: 31)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLA	NM_001045556.3	c.61+3976T>A		intron_variant		ENST00000338087.10	NP_001039021.1
TG	NM_003235.5	c.7239+26101A>T		intron_variant		ENST00000220616.9	NP_003226.4
PTCSC1	NR_146773.1	n.1166A>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TG	ENST00000220616.9	c.7239+26101A>T		intron_variant		1	NM_003235.5	ENSP00000220616	P1
SLA	ENST00000338087.10	c.61+3976T>A		intron_variant		1	NM_001045556.3	ENSP00000337548	P1
PTCSC1	ENST00000664551.1	n.1166A>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79783 AN: 151878 Hom.: 21238 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.525 AC: 79872 AN: 151996 Hom.: 21273 Cov.: 31 AF XY: 0.526 AC XY: 39080 AN XY: 74272

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.535

Alfa AF: 0.503 Hom.: 2433

Bravo AF: 0.539

Asia WGS AF: 0.609 AC: 2114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.41

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: rs2702968; hg19: chr8-134068369;