rs886061163

Variant names:

• chr6-150368928-T-A
• rs886061163
• ENST00000229447.9:c.-104T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-150368928-T-A
• chr6-150368928-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000229447.9(IYD):​c.-104T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000939 in 1,065,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: IYD ENST00000229447.9 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.845
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000229447.9. 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
	IYD	NM_203395.3	MANE Select	c.-104T>A		upstream_gene	N/A	NP_981932.1	Q6PHW0-1
	IYD	NM_001164694.2		c.-104T>A		upstream_gene	N/A	NP_001158166.1	Q6PHW0-4
	IYD	NM_001164695.2		c.-104T>A		upstream_gene	N/A	NP_001158167.1	Q6PHW0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IYD	ENST00000229447.9	TSL:1	c.-104T>A		5_prime_UTR	Exon 1 of 6	ENSP00000229447.5	Q6PHW0-4
	IYD	ENST00000892602.1		c.-104T>A		5_prime_UTR	Exon 1 of 4	ENSP00000562661.1
	IYD	ENST00000344419.8	TSL:1 MANE Select	c.-104T>A		upstream_gene	N/A	ENSP00000343763.4	Q6PHW0-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.39e-7 AC: 1 AN: 1065516 Hom.: 0 Cov.: 15 AF XY: 0.00000182 AC XY: 1 AN XY: 548024

African (AFR) AF: 0.00 AC: 0 AN: 25632

American (AMR) AF: 0.00 AC: 0 AN: 44140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23598

East Asian (EAS) AF: 0.00 AC: 0 AN: 37736

South Asian (SAS) AF: 0.00 AC: 0 AN: 77690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4796

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 752076

Other (OTH) AF: 0.0000212 AC: 1 AN: 47104

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital hypothyroidism (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.49
DANN	Benign	0.72
PhyloP100		-0.84
PromoterAI		0.25	Neutral

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: rs886061163; hg19: chr6-150690064;