rs112076606

chr19-17883785-A-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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.63

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=-0.9).
• BP6: Variant 19-17883785-A-G is Benign according to our data. Variant chr19-17883785-A-G is described in ClinVar as [Benign]. Clinvar id is 256196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-17883785-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A5	NM_000453.3	c.1329+18A>G		intron_variant		ENST00000222248.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A5	ENST00000222248.4	c.1329+18A>G		intron_variant		1	NM_000453.3	P1
SLC5A5	ENST00000597109.1	n.328+18A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5450 AN: 143370 Hom.: 304 Cov.: 31

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

GnomAD3 exomes AF: 0.00941 AC: 2255 AN: 239576 Hom.: 114 AF XY: 0.00736 AC XY: 971 AN XY: 131942

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 SAS exome AF: 0.000164

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.: 32 AF XY: 0.00492 AC XY: 2645 AN XY: 537172

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.00925

Gnomad4 ASJ exome AF: 0.00616

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000176

Gnomad4 FIN exome AF: 0.0000240

Gnomad4 NFE exome AF: 0.000945

Gnomad4 OTH exome AF: 0.0141

GnomAD4 genome AF: 0.0381 AC: 5470 AN: 143502 Hom.: 307 Cov.: 31 AF XY: 0.0375 AC XY: 2617 AN XY: 69872

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0149

Gnomad4 ASJ AF: 0.00211

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000954

Gnomad4 OTH AF: 0.0250

Alfa AF: 0.0214 Hom.: 25

Bravo AF: 0.0414

Asia WGS AF: 0.00954 AC: 35 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.11
Dann	Benign	0.37

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: rs112076606; hg19: chr19-17994594;