dbSNP rs7578597: THADA:p.Thr1187Ala (chr2-43505684-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_022065.5(THADA):c.3559A>G(p.Thr1187Ala) variant causes a missense change. The variant allele was found at a frequency of 0.109 in 1,593,848 control chromosomes in the GnomAD database, including 11,113 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 0.14 ( 1998 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9115 hom. )

Consequence

THADA
NM_022065.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.85

Publications

249 publications found

Variant links:

Genes affected

THADA (HGNC:19217): (THADA armadillo repeat containing) This gene is the target of 2p21 choromosomal aberrations in benign thyroid adenomas. Single nucleotide polymorphisms (SNPs) in this gene may be associated with type 2 diabetes and polycystic ovary syndrome. The encoded protein is likely involved in the death receptor pathway and apoptosis. [provided by RefSeq, Sep 2016]

THADA 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 (MetaRNN=0.0019688606).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5 link	c.3559A>G	p.Thr1187Ala	missense_variant	Exon 24 of 38	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7 link	c.3559A>G	p.Thr1187Ala	missense_variant	Exon 24 of 38	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21313

AN:

152144

Hom.:

1986

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0812

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.00672

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.0481

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.0990

AC:

21766

AN:

219906

AF XY:

0.100

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.0564

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.00576

Gnomad FIN exome

AF:

0.0510

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.0960

GnomAD4 exome

AF:

0.106

AC:

153003

AN:

1441586

Hom.:

9115

Cov.:

AF XY:

0.107

AC XY:

76205

AN XY:

714672

show subpopulations

African (AFR)

AF:

0.268

AC:

8918

AN:

33284

American (AMR)

AF:

0.0585

AC:

2445

AN:

41790

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

3023

AN:

25678

East Asian (EAS)

AF:

0.00779

AC:

308

AN:

39514

South Asian (SAS)

AF:

0.135

AC:

11191

AN:

82904

European-Finnish (FIN)

AF:

0.0530

AC:

2780

AN:

52468

Middle Eastern (MID)

AF:

0.0720

AC:

413

AN:

5740

European-Non Finnish (NFE)

AF:

0.107

AC:

117948

AN:

1100458

Other (OTH)

AF:

0.100

AC:

5977

AN:

59750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

6376

12752

19128

25504

31880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4432

8864

13296

17728

22160

<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:

0.140

AC:

21364

AN:

152262

Hom.:

1998

Cov.:

AF XY:

0.134

AC XY:

9984

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.265

AC:

10992

AN:

41522

American (AMR)

AF:

0.0811

AC:

1241

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

442

AN:

3472

East Asian (EAS)

AF:

0.00674

AC:

AN:

5194

South Asian (SAS)

AF:

0.132

AC:

640

AN:

4832

European-Finnish (FIN)

AF:

0.0481

AC:

511

AN:

10618

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7188

AN:

68006

Other (OTH)

AF:

0.112

AC:

236

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

900

1800

2701

3601

4501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.116

Hom.:

5738

Bravo

AF:

0.146

TwinsUK

AF:

0.107

AC:

398

ALSPAC

AF:

0.115

AC:

444

ESP6500AA

AF:

0.260

AC:

968

ESP6500EA

AF:

0.110

AC:

897

ExAC

AF:

0.0971

AC:

11681

Asia WGS

AF:

0.0660

AC:

231

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.73

.;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

PhyloP100

4.9

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.094

Sift

Benign

0.089

T;T

Sift4G

Benign

0.080

T;T

Polyphen

0.17

B;B

Vest4

0.15

ClinPred

0.014

GERP RS

5.5

Varity_R

0.26

gMVP

0.52

Mutation Taster

=93/7

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