NM_000453.3:c.1330-15C>T

Variant names:

• chr19-17883835-C-T
• rs77947605
• NM_000453.3:c.1330-15C>T

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.1330-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 1,603,242 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (86 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (85 hom.)
• Consequence: SLC5A5 NM_000453.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.56
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-17883835-C-T is Benign according to our data. Variant chr19-17883835-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0627 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.1330-15C>T		intron	N/A	NP_000444.1
	SLC5A5	NM_001440707.1		c.1063-15C>T		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.1330-15C>T		intron	N/A	ENSP00000222248.2
	SLC5A5	ENST00000597109.1	TSL:4	n.329-15C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2893 AN: 152154 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000765

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00484 AC: 1068 AN: 220456 AF XY: 0.00377

Gnomad AFR exome AF: 0.0662

Gnomad AMR exome AF: 0.00438

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000503

Gnomad NFE exome AF: 0.000834

Gnomad OTH exome AF: 0.00383

GnomAD4 exome AF: 0.00242 AC: 3513 AN: 1450970 Hom.: 85 Cov.: 35 AF XY: 0.00216 AC XY: 1559 AN XY: 721106

African (AFR) AF: 0.0664 AC: 2201 AN: 33124

American (AMR) AF: 0.00495 AC: 217 AN: 43804

Ashkenazi Jewish (ASJ) AF: 0.00158 AC: 41 AN: 25872

East Asian (EAS) AF: 0.00 AC: 0 AN: 39194

South Asian (SAS) AF: 0.000129 AC: 11 AN: 85538

European-Finnish (FIN) AF: 0.0000196 AC: 1 AN: 51038

Middle Eastern (MID) AF: 0.00966 AC: 47 AN: 4864

European-Non Finnish (NFE) AF: 0.000602 AC: 667 AN: 1107780

Other (OTH) AF: 0.00549 AC: 328 AN: 59756

GnomAD4 genome AF: 0.0191 AC: 2904 AN: 152272 Hom.: 86 Cov.: 32 AF XY: 0.0184 AC XY: 1369 AN XY: 74468

African (AFR) AF: 0.0648 AC: 2690 AN: 41534

American (AMR) AF: 0.00836 AC: 128 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000765 AC: 52 AN: 68002

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.0134 Hom.: 10

Bravo AF: 0.0217

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.025
DANN	Benign	0.94
PhyloP100		-2.6
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: rs77947605; hg19: chr19-17994644;