NM_000453.3:c.1652-9G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000453.3(SLC5A5):c.1652-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,597,824 control chromosomes in the GnomAD database, including 38,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3029 hom., cov: 31)

Exomes 𝑓: 0.22 ( 35820 hom. )

Consequence

SLC5A5
NM_000453.3 intron

Scores

Splicing: ADA: 0.00005823

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.00600

Publications

12 publications found

Variant links:

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

SLC5A5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-17890877-G-A is Benign according to our data. Variant chr19-17890877-G-A is described in ClinVar as Benign. ClinVar VariationId is 256199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A5	NM_000453.3 link	c.1652-9G>A		intron_variant	Intron 13 of 14	ENST00000222248.4	NP_000444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A5	ENST00000222248.4 link	c.1652-9G>A		intron_variant	Intron 13 of 14	1	NM_000453.3	ENSP00000222248.2

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28314

AN:

151740

Hom.:

3026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.0945

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.0118

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.179

AC:

44669

AN:

249144

AF XY:

0.183

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.234

Gnomad EAS exome

AF:

0.00669

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.216

AC:

312877

AN:

1445966

Hom.:

35820

Cov.:

AF XY:

0.214

AC XY:

154331

AN XY:

720230

show subpopulations

African (AFR)

AF:

0.123

AC:

4069

AN:

33150

American (AMR)

AF:

0.122

AC:

5449

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

6034

AN:

26036

East Asian (EAS)

AF:

0.0258

AC:

1023

AN:

39628

South Asian (SAS)

AF:

0.130

AC:

11177

AN:

85910

European-Finnish (FIN)

AF:

0.246

AC:

13143

AN:

53358

Middle Eastern (MID)

AF:

0.256

AC:

1363

AN:

5314

European-Non Finnish (NFE)

AF:

0.235

AC:

258556

AN:

1098012

Other (OTH)

AF:

0.202

AC:

12063

AN:

59856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

11857

23713

35570

47426

59283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8614

17228

25842

34456

43070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.187

AC:

28336

AN:

151858

Hom.:

3029

Cov.:

AF XY:

0.185

AC XY:

13735

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.122

AC:

5039

AN:

41422

American (AMR)

AF:

0.167

AC:

2540

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

820

AN:

3468

East Asian (EAS)

AF:

0.0118

AC:

AN:

5168

South Asian (SAS)

AF:

0.121

AC:

580

AN:

4810

European-Finnish (FIN)

AF:

0.265

AC:

2795

AN:

10528

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.235

AC:

15945

AN:

67922

Other (OTH)

AF:

0.190

AC:

400

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1142

2285

3427

4570

5712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.218

Hom.:

5542

Bravo

AF:

0.176

Asia WGS

AF:

0.0890

AC:

309

AN:

3478

EpiCase

AF:

0.237

EpiControl

AF:

0.236

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Thyroid dyshormonogenesis 1

Benign:3

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.7

(source)

DANN

Benign

0.62

PhyloP100

-0.0060

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000058

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over