Variant 19-17872250-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000453.3(SLC5A5):c.-70C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 560,874 control chromosomes in the GnomAD database, including 914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 132 hom., cov: 32)

Exomes 𝑓: 0.068 ( 782 hom. )

Consequence

SLC5A5
NM_000453.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-17872250-C-T is Benign according to our data. Variant chr19-17872250-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 328529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SLC5A5	NM_000453.3 linkuse as main transcript	c.-70C>T	5_prime_UTR_variant	1/15	ENST00000222248.4	NP_000444.1
SLC5A5	XM_011528192.3 linkuse as main transcript	c.-70C>T	5_prime_UTR_variant	1/15		XP_011526494.1
SLC5A5	XM_011528193.4 linkuse as main transcript	c.-52+207C>T	intron_variant			XP_011526495.1
SLC5A5	XM_017027158.2 linkuse as main transcript	c.-52+207C>T	intron_variant			XP_016882647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A5	ENST00000222248.4 linkuse as main transcript	c.-70C>T		5_prime_UTR_variant	1/15	1	NM_000453.3	ENSP00000222248	P1

Frequencies

GnomAD3 genomes

AF:

0.0355

AC:

5222

AN:

146908

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00906

Gnomad AMI

AF:

0.0342

Gnomad AMR

AF:

0.0444

Gnomad ASJ

AF:

0.0577

Gnomad EAS

AF:

0.000437

Gnomad SAS

AF:

0.0634

Gnomad FIN

AF:

0.0372

Gnomad MID

AF:

0.0327

Gnomad NFE

AF:

0.0486

Gnomad OTH

AF:

0.0490

GnomAD4 exome

AF:

0.0678

AC:

28078

AN:

413836

Hom.:

782

Cov.:

AF XY:

0.0685

AC XY:

15356

AN XY:

224338

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.0409

Gnomad4 ASJ exome

AF:

0.0927

Gnomad4 EAS exome

AF:

0.000391

Gnomad4 SAS exome

AF:

0.0621

Gnomad4 FIN exome

AF:

0.0634

Gnomad4 NFE exome

AF:

0.0753

Gnomad4 OTH exome

AF:

0.0778

GnomAD4 genome

AF:

0.0355

AC:

5221

AN:

147038

Hom.:

132

Cov.:

AF XY:

0.0356

AC XY:

2552

AN XY:

71610

show subpopulations

Gnomad4 AFR

AF:

0.00901

Gnomad4 AMR

AF:

0.0444

Gnomad4 ASJ

AF:

0.0577

Gnomad4 EAS

AF:

0.000438

Gnomad4 SAS

AF:

0.0634

Gnomad4 FIN

AF:

0.0372

Gnomad4 NFE

AF:

0.0486

Gnomad4 OTH

AF:

0.0484

Alfa

AF:

0.0370

Hom.:

Bravo

AF:

0.0340

Asia WGS

AF:

0.0230

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Thyroid dyshormonogenesis 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.5

DANN

Benign

0.78

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