Genetic Variant IYD:c.*1198T>G (chr6-150399435-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.262

Publications

7 publications found

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 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

IYD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IYD	NM_203395.3 link	c.*1198T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000344419.8	NP_981932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IYD	ENST00000344419.8 link	c.*1198T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_203395.3	ENSP00000343763.4
IYD	ENST00000229447.9 link	c.*1298T>G		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000229447.5

Frequencies

GnomAD3 genomes

AF:

0.862

AC:

130984

AN:

151918

Hom.:

56931

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.964

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.964

AC:

108

AN:

112

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.862

AC:

131072

AN:

152036

Hom.:

56965

Cov.:

AF XY:

0.855

AC XY:

63540

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.762

AC:

31583

AN:

41470

American (AMR)

AF:

0.852

AC:

13032

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.869

AC:

3015

AN:

3470

East Asian (EAS)

AF:

0.792

AC:

4044

AN:

5108

South Asian (SAS)

AF:

0.794

AC:

3817

AN:

4808

European-Finnish (FIN)

AF:

0.883

AC:

9321

AN:

10562

Middle Eastern (MID)

AF:

0.901

AC:

265

AN:

294

European-Non Finnish (NFE)

AF:

0.931

AC:

63295

AN:

68006

Other (OTH)

AF:

0.873

AC:

1844

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

853

1706

2558

3411

4264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.907

Hom.:

249242

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

(source)

DANN

Benign

0.81

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over