rs73520745

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.1507G>A(p.Asp503Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,569,392 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 74 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 48 hom. )

Consequence

SLC5A5
NM_000453.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0520

Publications

5 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: G2P, PanelApp Australia, Ambry Genetics, 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 (MetaRNN=0.0018436909).

BP6

Variant 19-17884027-G-A is Benign according to our data. Variant chr19-17884027-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 328541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000453.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A5	NM_000453.3	MANE Select	c.1507G>A	p.Asp503Asn	missense	Exon 12 of 15	NP_000444.1	Q92911
	SLC5A5	NM_001440707.1		c.1240G>A	p.Asp414Asn	missense	Exon 13 of 16	NP_001427636.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A5	ENST00000222248.4	TSL:1 MANE Select	c.1507G>A	p.Asp503Asn	missense	Exon 12 of 15	ENSP00000222248.2	Q92911
	SLC5A5	ENST00000597109.1	TSL:4	n.506G>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2466

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00381

AC:

659

AN:

173058

AF XY:

0.00297

show subpopulations

Gnomad AFR exome

AF:

0.0562

Gnomad AMR exome

AF:

0.00245

Gnomad ASJ exome

AF:

0.00283

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00216

GnomAD4 exome

AF:

0.00168

AC:

2375

AN:

1417082

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1009

AN XY:

701264

show subpopulations

African (AFR)

AF:

0.0554

AC:

1818

AN:

32790

American (AMR)

AF:

0.00326

AC:

123

AN:

37754

Ashkenazi Jewish (ASJ)

AF:

0.00320

AC:

AN:

25306

East Asian (EAS)

AF:

0.00

AC:

AN:

37880

South Asian (SAS)

AF:

0.0000989

AC:

AN:

80908

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46150

Middle Eastern (MID)

AF:

0.00193

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.0000687

AC:

AN:

1091712

Other (OTH)

AF:

0.00440

AC:

259

AN:

58878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

127

253

380

506

633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.0162

AC:

2472

AN:

152310

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1178

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0565

AC:

2348

AN:

41576

American (AMR)

AF:

0.00575

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68012

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

115

230

346

461

576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00670

Hom.:

Bravo

AF:

0.0184

ESP6500AA

AF:

0.0416

AC:

182

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00366

AC:

432

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

SLC5A5-related disorder (1)

Thyroid dyshormonogenesis 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.5

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.015

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-0.66

PhyloP100

-0.052

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.18

REVEL

Benign

0.19

Sift

Benign

0.49

Sift4G

Benign

0.65

Polyphen

0.35

Vest4

0.11

MVP

0.18

MPC

0.19

ClinPred

0.0010

GERP RS

-3.2

Varity_R

0.029

gMVP

0.40

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over