Variant 6-150389311-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.767

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IYD	NM_203395.3 linkuse as main transcript	c.179-41G>A		intron_variant		ENST00000344419.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IYD	ENST00000344419.8 linkuse as main transcript	c.179-41G>A		intron_variant		1	NM_203395.3	P1	Q6PHW0-1

Frequencies

GnomAD3 genomes

AF:

0.0839

AC:

12763

AN:

152116

Hom.:

877

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0941

AC:

23307

AN:

247678

Hom.:

2017

AF XY:

0.0893

AC XY:

11965

AN XY:

134046

show subpopulations

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 SAS exome

AF:

0.129

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.:

AF XY:

0.0575

AC XY:

39581

AN XY:

688424

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.175

Gnomad4 ASJ exome

AF:

0.0519

Gnomad4 EAS exome

AF:

0.312

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.0219

Gnomad4 NFE exome

AF:

0.0339

Gnomad4 OTH exome

AF:

0.0708

GnomAD4 genome

AF:

0.0839

AC:

12777

AN:

152236

Hom.:

881

Cov.:

AF XY:

0.0856

AC XY:

6369

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.0531

Gnomad4 EAS

AF:

0.307

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.0210

Gnomad4 NFE

AF:

0.0359

Gnomad4 OTH

AF:

0.0888

Alfa

AF:

0.0626

Hom.:

Bravo

AF:

0.0957

Asia WGS

AF:

0.210

AC:

733

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.5

DANN

Benign

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over