chr6-150389311-G-A

Variant names:

• chr6-150389311-G-A
• rs9397944
• NM_203395.3:c.179-41G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_203395.3(IYD):​c.179-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 1,525,250 control chromosomes in the GnomAD database, including 5,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.084 (881 hom., cov: 32)
  • Exomes 𝑓: 0.056 (4746 hom.)
• Consequence: IYD NM_203395.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.767
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-150389311-G-A is Benign according to our data. Variant chr6-150389311-G-A is described in ClinVar as Benign. ClinVar VariationId is 1286156.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IYD	NM_203395.3	MANE Select	c.179-41G>A		intron	N/A	NP_981932.1	Q6PHW0-1
	IYD	NM_001164694.2		c.179-41G>A		intron	N/A	NP_001158166.1	Q6PHW0-4
	IYD	NM_001164695.2		c.179-41G>A		intron	N/A	NP_001158167.1	Q6PHW0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IYD	ENST00000344419.8	TSL:1 MANE Select	c.179-41G>A		intron	N/A	ENSP00000343763.4	Q6PHW0-1
	IYD	ENST00000229447.9	TSL:1	c.179-41G>A		intron	N/A	ENSP00000229447.5	Q6PHW0-4
	IYD	ENST00000392255.7	TSL:1	c.179-41G>A		intron	N/A	ENSP00000376084.3	C9JXJ9

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12763 AN: 152116 Hom.: 877 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0359

Gnomad OTH AF: 0.0883

GnomAD2 exomes AF: 0.0941 AC: 23307 AN: 247678 AF XY: 0.0893

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.0536

Gnomad EAS exome AF: 0.307

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.0344

Gnomad OTH exome AF: 0.0692

GnomAD4 exome AF: 0.0563 AC: 77330 AN: 1373014 Hom.: 4746 Cov.: 21 AF XY: 0.0575 AC XY: 39581 AN XY: 688424

African (AFR) AF: 0.141 AC: 4449 AN: 31648

American (AMR) AF: 0.175 AC: 7787 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 1325 AN: 25534

East Asian (EAS) AF: 0.312 AC: 12228 AN: 39166

South Asian (SAS) AF: 0.130 AC: 10923 AN: 84060

European-Finnish (FIN) AF: 0.0219 AC: 1159 AN: 52920

Middle Eastern (MID) AF: 0.0689 AC: 373 AN: 5412

European-Non Finnish (NFE) AF: 0.0339 AC: 35016 AN: 1032338

Other (OTH) AF: 0.0708 AC: 4070 AN: 57498

GnomAD4 genome AF: 0.0839 AC: 12777 AN: 152236 Hom.: 881 Cov.: 32 AF XY: 0.0856 AC XY: 6369 AN XY: 74436

African (AFR) AF: 0.137 AC: 5673 AN: 41534

American (AMR) AF: 0.107 AC: 1629 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 184 AN: 3468

East Asian (EAS) AF: 0.307 AC: 1589 AN: 5176

South Asian (SAS) AF: 0.138 AC: 665 AN: 4820

European-Finnish (FIN) AF: 0.0210 AC: 223 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0359 AC: 2441 AN: 68020

Other (OTH) AF: 0.0888 AC: 188 AN: 2116

Alfa AF: 0.0626 Hom.: 85

Bravo AF: 0.0957

Asia WGS AF: 0.210 AC: 733 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.67
PhyloP100		0.77
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: rs9397944; hg19: chr6-150710447; COSMIC: COSV57601350; COSMIC: COSV57601350;