19-17893553-C-G

Variant names:

• chr19-17893553-C-G
• rs7250346
• NM_000453.3:c.1768-160C>G

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.1768-160C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,928 control chromosomes in the GnomAD database, including 10,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.33 (10306 hom., cov: 31)
• Consequence: SLC5A5 NM_000453.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0770

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=-1.0).
• BP6: Variant 19-17893553-C-G is Benign according to our data. Variant chr19-17893553-C-G is described in ClinVar as [Benign]. Clinvar id is 1231310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A5	NM_000453.3	c.1768-160C>G		intron_variant	Intron 14 of 14	ENST00000222248.4	NP_000444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A5	ENST00000222248.4	c.1768-160C>G		intron_variant	Intron 14 of 14	1	NM_000453.3	ENSP00000222248.2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49512 AN: 151810 Hom.: 10267 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.294

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.327 AC: 49608 AN: 151928 Hom.: 10306 Cov.: 31 AF XY: 0.320 AC XY: 23734 AN XY: 74266

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.296

Alfa AF: 0.160 Hom.: 325

Bravo AF: 0.336

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.1
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7250346; hg19: chr19-18004362;