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

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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	Q6YHU6-1

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		Q6YHU6-1

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

GnomAD3 exomes

AF:

0.0990

AC:

21766

AN:

219906

Hom.:

1424

AF XY:

0.100

AC XY:

11828

AN XY:

117810

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 SAS exome

AF:

0.134

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

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.0585

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.00779

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.0530

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.100

GnomAD4 genome

AF:

0.140

AC:

21364

AN:

152262

Hom.:

1998

Cov.:

AF XY:

0.134

AC XY:

9984

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.265

Gnomad4 AMR

AF:

0.0811

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.00674

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.0481

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.110

Hom.:

2592

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

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over