19-17883832-C-G

Variant names:

• chr19-17883832-C-G
• rs369522814
• NM_000453.3:c.1330-18C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000453.3(SLC5A5):​c.1330-18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,603,940 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (13 hom.)
• Consequence: SLC5A5 NM_000453.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.348
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• thyroid dyshormonogenesis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial thyroid dyshormonogenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 19-17883832-C-G is Benign according to our data. Variant chr19-17883832-C-G is described in ClinVar as Benign. ClinVar VariationId is 256198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00764 (1163/152306) while in subpopulation AFR AF = 0.0265 (1102/41558). AF 95% confidence interval is 0.0252. There are 12 homozygotes in GnomAd4. There are 547 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000453.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A5	NM_000453.3	MANE Select	c.1330-18C>G		intron	N/A	NP_000444.1	Q92911
	SLC5A5	NM_001440707.1		c.1063-18C>G		intron	N/A	NP_001427636.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A5	ENST00000222248.4	TSL:1 MANE Select	c.1330-18C>G		intron	N/A	ENSP00000222248.2	Q92911
	SLC5A5	ENST00000597109.1	TSL:4	n.329-18C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00763 AC: 1161 AN: 152188 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00197 AC: 438 AN: 222570 AF XY: 0.00157

Gnomad AFR exome AF: 0.0289

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000271

Gnomad OTH exome AF: 0.000725

GnomAD4 exome AF: 0.000909 AC: 1319 AN: 1451634 Hom.: 13 Cov.: 35 AF XY: 0.000779 AC XY: 562 AN XY: 721512

African (AFR) AF: 0.0282 AC: 935 AN: 33156

American (AMR) AF: 0.00166 AC: 73 AN: 43926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25888

East Asian (EAS) AF: 0.00 AC: 0 AN: 39242

South Asian (SAS) AF: 0.0000584 AC: 5 AN: 85590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51098

Middle Eastern (MID) AF: 0.00493 AC: 24 AN: 4864

European-Non Finnish (NFE) AF: 0.000135 AC: 150 AN: 1108072

Other (OTH) AF: 0.00221 AC: 132 AN: 59798

GnomAD4 genome AF: 0.00764 AC: 1163 AN: 152306 Hom.: 12 Cov.: 32 AF XY: 0.00734 AC XY: 547 AN XY: 74482

African (AFR) AF: 0.0265 AC: 1102 AN: 41558

American (AMR) AF: 0.00268 AC: 41 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68014

Other (OTH) AF: 0.00237 AC: 5 AN: 2108

Alfa AF: 0.000690 Hom.: 0

Bravo AF: 0.00910

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.0
DANN	Benign	0.66
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs369522814; hg19: chr19-17994641;