19-17872250-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000453.3(SLC5A5):c.-70C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 560,874 control chromosomes in the GnomAD database, including 914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (132 hom., cov: 32)
  • Exomes 𝑓: 0.068 (782 hom.)
• Consequence: SLC5A5 NM_000453.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.09

Genes affected

SLC5A5 (HGNC:11040): (solute carrier family 5 member 5) This gene encodes a member of the sodium glucose cotransporter family. The encoded protein is responsible for the uptake of iodine in tissues such as the thyroid and lactating breast tissue. The iodine taken up by the thyroid is incorporated into the metabolic regulators triiodothyronine (T3) and tetraiodothyronine (T4). Mutations in this gene are associated with thyroid dyshormonogenesis 1.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-17872250-C-T is Benign according to our data. Variant chr19-17872250-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 328529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A5	NM_000453.3	c.-70C>T		5_prime_UTR_variant	1/15	ENST00000222248.4
SLC5A5	XM_011528192.3	c.-70C>T		5_prime_UTR_variant	1/15
SLC5A5	XM_011528193.4	c.-52+207C>T		intron_variant
SLC5A5	XM_017027158.2	c.-52+207C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A5	ENST00000222248.4	c.-70C>T		5_prime_UTR_variant	1/15	1	NM_000453.3	P1

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5222 AN: 146908 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.00906

Gnomad AMI AF: 0.0342

Gnomad AMR AF: 0.0444

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.000437

Gnomad SAS AF: 0.0634

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.0327

Gnomad NFE AF: 0.0486

Gnomad OTH AF: 0.0490

GnomAD4 exome AF: 0.0678 AC: 28078 AN: 413836 Hom.: 782 Cov.: 9 AF XY: 0.0685 AC XY: 15356 AN XY: 224338

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.0409

Gnomad4 ASJ exome AF: 0.0927

Gnomad4 EAS exome AF: 0.000391

Gnomad4 SAS exome AF: 0.0621

Gnomad4 FIN exome AF: 0.0634

Gnomad4 NFE exome AF: 0.0753

Gnomad4 OTH exome AF: 0.0778

GnomAD4 genome AF: 0.0355 AC: 5221 AN: 147038 Hom.: 132 Cov.: 32 AF XY: 0.0356 AC XY: 2552 AN XY: 71610

Gnomad4 AFR AF: 0.00901

Gnomad4 AMR AF: 0.0444

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.000438

Gnomad4 SAS AF: 0.0634

Gnomad4 FIN AF: 0.0372

Gnomad4 NFE AF: 0.0486

Gnomad4 OTH AF: 0.0484

Alfa AF: 0.0370 Hom.: 22

Bravo AF: 0.0340

Asia WGS AF: 0.0230 AC: 81 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial thyroid dyshormonogenesis 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.5
Dann	Benign	0.78

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: rs118133504; hg19: chr19-17983059;