19-17872266-C-T

Position:

• chr19-17872266-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000453.3(SLC5A5):​c.-54C>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 0.00356 in 1,304,458 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (76 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (52 hom.)
• Consequence: SLC5A5 NM_000453.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.25

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-17872266-C-T is Benign according to our data. Variant chr19-17872266-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 803544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A5	NM_000453.3	c.-54C>T		5_prime_UTR_variant	1/15	ENST00000222248.4	NP_000444.1
SLC5A5	XM_011528192.3	c.-54C>T		5_prime_UTR_variant	1/15		XP_011526494.1
SLC5A5	XM_011528193.4	c.-52+223C>T		intron_variant			XP_011526495.1
SLC5A5	XM_017027158.2	c.-52+223C>T		intron_variant			XP_016882647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A5	ENST00000222248.4	c.-54C>T		5_prime_UTR_variant	1/15	1	NM_000453.3	ENSP00000222248	P1

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2518 AN: 152018 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00714

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00183 AC: 2111 AN: 1152326 Hom.: 52 Cov.: 16 AF XY: 0.00155 AC XY: 896 AN XY: 579120

Gnomad4 AFR exome AF: 0.0555

Gnomad4 AMR exome AF: 0.00350

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000539

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000266

Gnomad4 OTH exome AF: 0.00475

GnomAD4 genome AF: 0.0166 AC: 2529 AN: 152132 Hom.: 76 Cov.: 32 AF XY: 0.0163 AC XY: 1216 AN XY: 74388

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.00713

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0146 Hom.: 7

Bravo AF: 0.0188

Asia WGS AF: 0.00433 AC: 15 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Thyroid dyshormonogenesis 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	Aug 22, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 27, 2021

This variant is associated with the following publications: (PMID: 21565787) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs112077649; hg19: chr19-17983075;