6-150395560-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001164694.2(IYD):c.793T>C(p.Cys265Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 1,537,026 control chromosomes in the GnomAD database, including 633,605 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C265Y) has been classified as Benign.

Frequency

Genomes: 𝑓 0.91 ( 63206 hom., cov: 33)

Exomes 𝑓: 0.91 ( 570399 hom. )

Consequence

IYD
NM_001164694.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.97

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.011365E-7).

BP6

Variant 6-150395560-T-C is Benign according to our data. Variant chr6-150395560-T-C is described in ClinVar as [Benign]. Clinvar id is 257584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-150395560-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IYD	NM_203395.3 link	c.687+1305T>C		intron_variant	Intron 4 of 4	ENST00000344419.8	NP_981932.1	Q6PHW0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IYD	ENST00000344419.8 link	c.687+1305T>C		intron_variant	Intron 4 of 4	1	NM_203395.3	ENSP00000343763.4		Q6PHW0-1

Frequencies

GnomAD3 genomes

AF:

0.910

AC:

138502

AN:

152180

Hom.:

63160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.958

Gnomad AMI

AF:

0.909

Gnomad AMR

AF:

0.866

Gnomad ASJ

AF:

0.854

Gnomad EAS

AF:

0.794

Gnomad SAS

AF:

0.808

Gnomad FIN

AF:

0.871

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.916

Gnomad OTH

AF:

0.904

GnomAD3 exomes

AF:

0.878

AC:

126813

AN:

144376

Hom.:

55932

AF XY:

0.873

AC XY:

67322

AN XY:

77094

show subpopulations

Gnomad AFR exome

AF:

0.964

Gnomad AMR exome

AF:

0.867

Gnomad ASJ exome

AF:

0.857

Gnomad EAS exome

AF:

0.798

Gnomad SAS exome

AF:

0.805

Gnomad FIN exome

AF:

0.869

Gnomad NFE exome

AF:

0.918

Gnomad OTH exome

AF:

0.894

GnomAD4 exome

AF:

0.907

AC:

1255419

AN:

1384728

Hom.:

570399

Cov.:

AF XY:

0.903

AC XY:

617049

AN XY:

683316

show subpopulations

Gnomad4 AFR exome

AF:

0.961

Gnomad4 AMR exome

AF:

0.866

Gnomad4 ASJ exome

AF:

0.860

Gnomad4 EAS exome

AF:

0.770

Gnomad4 SAS exome

AF:

0.806

Gnomad4 FIN exome

AF:

0.869

Gnomad4 NFE exome

AF:

0.921

Gnomad4 OTH exome

AF:

0.898

GnomAD4 genome

AF:

0.910

AC:

138605

AN:

152298

Hom.:

63206

Cov.:

AF XY:

0.903

AC XY:

67274

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.958

Gnomad4 AMR

AF:

0.866

Gnomad4 ASJ

AF:

0.854

Gnomad4 EAS

AF:

0.795

Gnomad4 SAS

AF:

0.808

Gnomad4 FIN

AF:

0.871

Gnomad4 NFE

AF:

0.916

Gnomad4 OTH

AF:

0.904

Alfa

AF:

0.907

Hom.:

72984

Bravo

AF:

0.915

TwinsUK

AF:

0.929

AC:

3443

ALSPAC

AF:

0.917

AC:

3534

ESP6500AA

AF:

0.956

AC:

1323

ESP6500EA

AF:

0.906

AC:

2882

ExAC

AF:

0.857

AC:

18713

Asia WGS

AF:

0.808

AC:

2811

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Iodotyrosine deiodination defect

Benign:1

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.14

DANN

Benign

0.26

DEOGEN2

Benign

0.013

.;.;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.26

T;T;T

MetaRNN

Benign

9.0e-7

T;T;T

MetaSVM

Benign

-0.89

PrimateAI

Benign

0.26

PROVEAN

Benign

1.5

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.43

T;T;T

Sift4G

Benign

0.36

T;T;T

Vest4

0.13

MPC

0.10

ClinPred

0.0030

GERP RS

-6.1

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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