NM_000453.3:c.*226T>C

Variant names:

• chr19-17894103-T-C
• rs12327843
• NM_000453.3:c.*226T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000453.3(SLC5A5):​c.*226T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 517,946 control chromosomes in the GnomAD database, including 13,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3961 hom., cov: 30)
  • Exomes 𝑓: 0.21 (9407 hom.)
• Consequence: SLC5A5 NM_000453.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.04
• Publications: 10 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=-0.94).
• BP6: Variant 19-17894103-T-C is Benign according to our data. Variant chr19-17894103-T-C is described in ClinVar as Benign. ClinVar VariationId is 328548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

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.*226T>C		3_prime_UTR	Exon 15 of 15	NP_000444.1	Q92911
	SLC5A5	NM_001440707.1		c.*226T>C		3_prime_UTR	Exon 16 of 16	NP_001427636.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A5	ENST00000222248.4	TSL:1 MANE Select	c.*226T>C		3_prime_UTR	Exon 15 of 15	ENSP00000222248.2	Q92911

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33295 AN: 151078 Hom.: 3949 Cov.: 30

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.214 AC: 78500 AN: 366778 Hom.: 9407 Cov.: 3 AF XY: 0.209 AC XY: 40518 AN XY: 193646

African (AFR) AF: 0.219 AC: 2175 AN: 9942

American (AMR) AF: 0.154 AC: 2212 AN: 14334

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 2922 AN: 11218

East Asian (EAS) AF: 0.0322 AC: 760 AN: 23636

South Asian (SAS) AF: 0.114 AC: 4358 AN: 38064

European-Finnish (FIN) AF: 0.269 AC: 6420 AN: 23890

Middle Eastern (MID) AF: 0.241 AC: 382 AN: 1588

European-Non Finnish (NFE) AF: 0.245 AC: 54580 AN: 222988

Other (OTH) AF: 0.222 AC: 4691 AN: 21118

GnomAD4 genome AF: 0.221 AC: 33350 AN: 151168 Hom.: 3961 Cov.: 30 AF XY: 0.218 AC XY: 16097 AN XY: 73836

African (AFR) AF: 0.222 AC: 9112 AN: 41084

American (AMR) AF: 0.188 AC: 2855 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3464

East Asian (EAS) AF: 0.0115 AC: 59 AN: 5146

South Asian (SAS) AF: 0.112 AC: 536 AN: 4794

European-Finnish (FIN) AF: 0.271 AC: 2799 AN: 10338

Middle Eastern (MID) AF: 0.260 AC: 75 AN: 288

European-Non Finnish (NFE) AF: 0.243 AC: 16464 AN: 67862

Other (OTH) AF: 0.224 AC: 470 AN: 2102

Alfa AF: 0.232 Hom.: 12962

Bravo AF: 0.216

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Thyroid dyshormonogenesis 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.075
DANN	Benign	0.29
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs12327843; hg19: chr19-18004912;