dbSNP rs112076606: SLC5A5:c.1329+18A>G (chr19-17883785-A-G) – ACMG Classification: Benign (-20 pts)

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.1329+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00961 in 1,206,290 control chromosomes in the GnomAD database, including 591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 307 hom., cov: 31)

Exomes 𝑓: 0.0058 ( 284 hom. )

Consequence

SLC5A5
NM_000453.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.63

Publications

2 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 (BayesDel_noAF=-0.9).

BP6

Variant 19-17883785-A-G is Benign according to our data. Variant chr19-17883785-A-G is described in ClinVar as Benign. ClinVar VariationId is 256196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 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.1329+18A>G		intron	N/A	NP_000444.1	Q92911
	SLC5A5	NM_001440707.1		c.1062+18A>G		intron	N/A	NP_001427636.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A5	ENST00000222248.4	TSL:1 MANE Select	c.1329+18A>G		intron	N/A	ENSP00000222248.2	Q92911
	SLC5A5	ENST00000597109.1	TSL:4	n.328+18A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0380

AC:

5450

AN:

143370

Hom.:

304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.00211

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000508

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00980

Gnomad NFE

AF:

0.000954

Gnomad OTH

AF:

0.0252

GnomAD2 exomes

AF:

0.00941

AC:

2255

AN:

239576

AF XY:

0.00736

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.00717

Gnomad ASJ exome

AF:

0.00409

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.00115

Gnomad OTH exome

AF:

0.00614

GnomAD4 exome

AF:

0.00576

AC:

6122

AN:

1062788

Hom.:

284

Cov.:

AF XY:

0.00492

AC XY:

2645

AN XY:

537172

show subpopulations

African (AFR)

AF:

0.160

AC:

4212

AN:

26346

American (AMR)

AF:

0.00925

AC:

376

AN:

40642

Ashkenazi Jewish (ASJ)

AF:

0.00616

AC:

122

AN:

19812

East Asian (EAS)

AF:

0.00

AC:

AN:

28654

South Asian (SAS)

AF:

0.000176

AC:

AN:

79464

European-Finnish (FIN)

AF:

0.0000240

AC:

AN:

41722

Middle Eastern (MID)

AF:

0.0138

AC:

AN:

4210

European-Non Finnish (NFE)

AF:

0.000945

AC:

736

AN:

779150

Other (OTH)

AF:

0.0141

AC:

603

AN:

42788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

265

530

794

1059

1324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<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:

0.0381

AC:

5470

AN:

143502

Hom.:

307

Cov.:

AF XY:

0.0375

AC XY:

2617

AN XY:

69872

show subpopulations

African (AFR)

AF:

0.127

AC:

5131

AN:

40260

American (AMR)

AF:

0.0149

AC:

217

AN:

14584

Ashkenazi Jewish (ASJ)

AF:

0.00211

AC:

AN:

3324

East Asian (EAS)

AF:

0.00

AC:

AN:

4106

South Asian (SAS)

AF:

0.00

AC:

AN:

3952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9066

Middle Eastern (MID)

AF:

0.00704

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000954

AC:

AN:

65018

Other (OTH)

AF:

0.0250

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

223

447

670

894

1117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0246

Hom.:

Bravo

AF:

0.0414

Asia WGS

AF:

0.00954

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.11

(source)

DANN

Benign

0.37

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(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