Variant 19-17872296-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000453.3(SLC5A5):c.-24C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,541,136 control chromosomes in the GnomAD database, including 169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.019 ( 91 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 78 hom. )

Consequence

SLC5A5
NM_000453.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.151

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-17872296-C-A is Benign according to our data. Variant chr19-17872296-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 328532.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SLC5A5	NM_000453.3 linkuse as main transcript	c.-24C>A	5_prime_UTR_variant	1/15	ENST00000222248.4
SLC5A5	XM_011528192.3 linkuse as main transcript	c.-24C>A	5_prime_UTR_variant	1/15
SLC5A5	XM_011528193.4 linkuse as main transcript	c.-51-240C>A	intron_variant
SLC5A5	XM_017027158.2 linkuse as main transcript	c.-51-240C>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A5	ENST00000222248.4 linkuse as main transcript	c.-24C>A		5_prime_UTR_variant	1/15	1	NM_000453.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2854

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0649

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00759

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:

0.000221

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00437

AC:

752

AN:

172000

Hom.:

AF XY:

0.00334

AC XY:

313

AN XY:

93638

show subpopulations

Gnomad AFR exome

AF:

0.0640

Gnomad AMR exome

AF:

0.00322

Gnomad ASJ exome

AF:

0.00295

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000409

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000292

Gnomad OTH exome

AF:

0.00239

GnomAD4 exome

AF:

0.00200

AC:

2778

AN:

1388958

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1180

AN XY:

687728

show subpopulations

Gnomad4 AFR exome

AF:

0.0662

Gnomad4 AMR exome

AF:

0.00411

Gnomad4 ASJ exome

AF:

0.00324

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000906

Gnomad4 OTH exome

AF:

0.00515

GnomAD4 genome

AF:

0.0188

AC:

2860

AN:

152178

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1367

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0649

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.0214

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial thyroid dyshormonogenesis 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.3

DANN

Benign

0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over