NM_203395.3:c.*1198T>G

Variant names:

• chr6-150399435-T-G
• rs601223
• NM_203395.3:c.*1198T>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.*1198T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,160 control chromosomes in the GnomAD database, including 57,022 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 0.86 (56965 hom., cov: 31)
  • Exomes 𝑓: 0.96 (57 hom.)
• Consequence: IYD NM_203395.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203395.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IYD	NM_203395.3	MANE Select	c.*1198T>G		3_prime_UTR	Exon 5 of 5	NP_981932.1
	IYD	NR_134655.2		n.2261T>G		non_coding_transcript_exon	Exon 6 of 6
	IYD	NM_001164694.2		c.*1298T>G		3_prime_UTR	Exon 6 of 6	NP_001158166.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IYD	ENST00000344419.8	TSL:1 MANE Select	c.*1198T>G		3_prime_UTR	Exon 5 of 5	ENSP00000343763.4
	IYD	ENST00000229447.9	TSL:1	c.*1298T>G		3_prime_UTR	Exon 6 of 6	ENSP00000229447.5

Frequencies

GnomAD3 genomes AF: 0.862 AC: 130984 AN: 151918 Hom.: 56931 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.873

GnomAD4 exome AF: 0.960 AC: 119 AN: 124 Hom.: 57 Cov.: 0 AF XY: 0.964 AC XY: 81 AN XY: 84

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.964 AC: 108 AN: 112

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.862 AC: 131072 AN: 152036 Hom.: 56965 Cov.: 31 AF XY: 0.855 AC XY: 63540 AN XY: 74288

African (AFR) AF: 0.762 AC: 31583 AN: 41470

American (AMR) AF: 0.852 AC: 13032 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3015 AN: 3470

East Asian (EAS) AF: 0.792 AC: 4044 AN: 5108

South Asian (SAS) AF: 0.794 AC: 3817 AN: 4808

European-Finnish (FIN) AF: 0.883 AC: 9321 AN: 10562

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63295 AN: 68006

Other (OTH) AF: 0.873 AC: 1844 AN: 2112

Alfa AF: 0.907 Hom.: 249242

Bravo AF: 0.859

Asia WGS AF: 0.796 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	9.2
DANN	Benign	0.81
PhyloP100		0.26
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: rs601223; hg19: chr6-150720571;