6-150399435-T-G

Position:

• chr6-150399435-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IYD	NM_203395.3	c.*1198T>G		3_prime_UTR_variant	5/5	ENST00000344419.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IYD	ENST00000344419.8	c.*1198T>G		3_prime_UTR_variant	5/5	1	NM_203395.3	P1
IYD	ENST00000229447.9	c.*1298T>G		3_prime_UTR_variant	6/6	1

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

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.964

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.873

Alfa AF: 0.915 Hom.: 108985

Bravo AF: 0.859

Asia WGS AF: 0.796 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	9.2
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs601223; hg19: chr6-150720571;