NM_000453.3(SLC5A5):c.1546C>T (p.Arg516Ter) AND Thyroid dyshormonogenesis 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 23, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003152944.1

Allele description [Variation Report for NM_000453.3(SLC5A5):c.1546C>T (p.Arg516Ter)]

NM_000453.3(SLC5A5):c.1546C>T (p.Arg516Ter)

Gene:

SLC5A5:solute carrier family 5 member 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.11

Genomic location:

Preferred name:

NM_000453.3(SLC5A5):c.1546C>T (p.Arg516Ter)

HGVS:

NC_000019.10:g.17888350C>T
NG_012930.1:g.21378C>T
NM_000453.3:c.1546C>TMANE SELECT
NP_000444.1:p.Arg516Ter
NC_000019.9:g.17999159C>T

Protein change:

R516*

Molecular consequence:

NM_000453.3:c.1546C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Thyroid dyshormonogenesis 1
Synonyms:: HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 1; IODINE ACCUMULATION, TRANSPORT, OR TRAPPING DEFECT; THYROID HORMONOGENESIS, GENETIC DEFECT IN, 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0020716; MedGen: C1848805; Orphanet: 95716; OMIM: 274400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003841516	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32805706, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003841516

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 23, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

First case of fetal goitrous hypothyroidism due to SLC5A5/NIS mutations.

Stoupa A, Al Hage Chehade G, Kariyawasam D, Tohier C, Bole-Feysot C, Nitschke P, Thibault H, Jullie ML, Polak M, Carré A.

Eur J Endocrinol. 2020 Nov;183(5):K1-K5. doi: 10.1530/EJE-20-0255.

PubMed [citation]

PMID:: 32805706

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV003841516.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with SLC5A- related disorder (PMID: 32805706). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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