19-17883764-A-T

Variant names:

• chr19-17883764-A-T
• rs73520743
• NM_000453.3:c.1326A>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000453.3(SLC5A5):​c.1326A>T​(p.Thr442Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 722,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T442T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC5A5 NM_000453.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.63
• Publications: 0 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• familial thyroid dyshormonogenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP7: Synonymous conserved (PhyloP=-6.63 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A5	NM_000453.3	c.1326A>T	p.Thr442Thr	synonymous_variant	Exon 11 of 15	ENST00000222248.4	NP_000444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A5	ENST00000222248.4	c.1326A>T	p.Thr442Thr	synonymous_variant	Exon 11 of 15	1	NM_000453.3	ENSP00000222248.2
SLC5A5	ENST00000597109.1	n.325A>T		non_coding_transcript_exon_variant	Exon 2 of 4	4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000138 AC: 1 AN: 722830 Hom.: 0 Cov.: 33 AF XY: 0.00000267 AC XY: 1 AN XY: 373920

African (AFR) AF: 0.00 AC: 0 AN: 21000

American (AMR) AF: 0.00 AC: 0 AN: 37188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14624

East Asian (EAS) AF: 0.0000672 AC: 1 AN: 14876

South Asian (SAS) AF: 0.00 AC: 0 AN: 73308

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 495640

Other (OTH) AF: 0.00 AC: 0 AN: 28798

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.47
PhyloP100		-6.6

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

Other links and lift over

dbSNP: rs73520743; hg19: chr19-17994573;