8-133038433-A-G

Position:

• chr8-133038433-A-G

Variant summary

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

The NM_001045556.3(SLA):​c.*91T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 973,326 control chromosomes in the GnomAD database, including 116,474 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 0.50 (19528 hom., cov: 32)
  • Exomes 𝑓: 0.48 (96946 hom.)
• Consequence: SLA NM_001045556.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLA	NM_001045556.3	c.*91T>C		3_prime_UTR_variant	9/9	ENST00000338087.10	NP_001039021.1
TG	NM_003235.5	c.7239+8410A>G		intron_variant		ENST00000220616.9	NP_003226.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLA	ENST00000338087.10	c.*91T>C		3_prime_UTR_variant	9/9	1	NM_001045556.3	ENSP00000337548	P1
TG	ENST00000220616.9	c.7239+8410A>G		intron_variant		1	NM_003235.5	ENSP00000220616	P1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75827 AN: 151934 Hom.: 19509 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.477 AC: 391604 AN: 821276 Hom.: 96946 Cov.: 11 AF XY: 0.474 AC XY: 203884 AN XY: 430050

Gnomad4 AFR exome AF: 0.574

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.561

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.491

Gnomad4 NFE exome AF: 0.512

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.499 AC: 75871 AN: 152050 Hom.: 19528 Cov.: 32 AF XY: 0.492 AC XY: 36562 AN XY: 74312

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.501

Alfa AF: 0.512 Hom.: 19877

Bravo AF: 0.498

Asia WGS AF: 0.297 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.16
DANN	Benign	0.56

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: rs3739266; hg19: chr8-134050678; COSMIC: COSV55069926;