rs12327843

Variant names:

• chr19-17894103-T-C
• rs12327843
• NM_000453.3:c.*226T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-17894103-T-C
• chr19-17894103-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000453.3(SLC5A5):​c.*226T>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 0.216 in 517,946 control chromosomes in the GnomAD database, including 13,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3961 hom., cov: 30)
  • Exomes 𝑓: 0.21 (9407 hom.)
• Consequence: SLC5A5 NM_000453.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.04
• Publications: 10 publications found

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]

SLC5A5 Gene-Disease associations (from GenCC):

• thyroid dyshormonogenesis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• familial thyroid dyshormonogenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-17894103-T-C is Benign according to our data. Variant chr19-17894103-T-C is described in ClinVar as Benign. ClinVar VariationId is 328548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A5	NM_000453.3	c.*226T>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000222248.4	NP_000444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A5	ENST00000222248.4	c.*226T>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_000453.3	ENSP00000222248.2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33295 AN: 151078 Hom.: 3949 Cov.: 30

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.214 AC: 78500 AN: 366778 Hom.: 9407 Cov.: 3 AF XY: 0.209 AC XY: 40518 AN XY: 193646

African (AFR) AF: 0.219 AC: 2175 AN: 9942

American (AMR) AF: 0.154 AC: 2212 AN: 14334

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 2922 AN: 11218

East Asian (EAS) AF: 0.0322 AC: 760 AN: 23636

South Asian (SAS) AF: 0.114 AC: 4358 AN: 38064

European-Finnish (FIN) AF: 0.269 AC: 6420 AN: 23890

Middle Eastern (MID) AF: 0.241 AC: 382 AN: 1588

European-Non Finnish (NFE) AF: 0.245 AC: 54580 AN: 222988

Other (OTH) AF: 0.222 AC: 4691 AN: 21118

GnomAD4 genome AF: 0.221 AC: 33350 AN: 151168 Hom.: 3961 Cov.: 30 AF XY: 0.218 AC XY: 16097 AN XY: 73836

African (AFR) AF: 0.222 AC: 9112 AN: 41084

American (AMR) AF: 0.188 AC: 2855 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3464

East Asian (EAS) AF: 0.0115 AC: 59 AN: 5146

South Asian (SAS) AF: 0.112 AC: 536 AN: 4794

European-Finnish (FIN) AF: 0.271 AC: 2799 AN: 10338

Middle Eastern (MID) AF: 0.260 AC: 75 AN: 288

European-Non Finnish (NFE) AF: 0.243 AC: 16464 AN: 67862

Other (OTH) AF: 0.224 AC: 470 AN: 2102

Alfa AF: 0.232 Hom.: 12962

Bravo AF: 0.216

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Thyroid dyshormonogenesis 1 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.075
DANN	Benign	0.29
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12327843; hg19: chr19-18004912;