rs1339110

Variant names:

• chr6-150377418-C-G
• rs1339110
• NM_203395.3:c.178+8209C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203395.3(IYD):​c.178+8209C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,122 control chromosomes in the GnomAD database, including 3,552 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (3552 hom., cov: 32)
• Consequence: IYD NM_203395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 0 publications found

Genes affected

IYD (HGNC:21071): (iodotyrosine deiodinase) This gene encodes an enzyme that catalyzes the oxidative NADPH-dependent deiodination of mono- and diiodotyrosine, which are the halogenated byproducts of thyroid hormone production. The N-terminus of the protein functions as a membrane anchor. Mutations in this gene cause congenital hypothyroidism due to dyshormonogenesis type 4, which is also referred to as deiodinase deficiency, or iodotyrosine dehalogenase deficiency, or thyroid hormonogenesis type 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

IYD Gene-Disease associations (from GenCC):

• thyroid dyshormonogenesis 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial thyroid dyshormonogenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IYD	NM_203395.3	c.178+8209C>G		intron_variant	Intron 1 of 4	ENST00000344419.8	NP_981932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IYD	ENST00000344419.8	c.178+8209C>G		intron_variant	Intron 1 of 4	1	NM_203395.3	ENSP00000343763.4

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23154 AN: 152004 Hom.: 3530 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.139

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.153 AC: 23219 AN: 152122 Hom.: 3552 Cov.: 32 AF XY: 0.152 AC XY: 11305 AN XY: 74358

African (AFR) AF: 0.378 AC: 15679 AN: 41446

American (AMR) AF: 0.134 AC: 2043 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 223 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1547 AN: 5168

South Asian (SAS) AF: 0.138 AC: 666 AN: 4810

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10620

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0351 AC: 2388 AN: 68004

Other (OTH) AF: 0.144 AC: 304 AN: 2112

Alfa AF: 0.0940 Hom.: 228

Bravo AF: 0.174

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.52
PhyloP100		-0.29
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: rs1339110; hg19: chr6-150698554;