Variant 2-43231001-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022065.5(THADA):c.5809T>G(p.Ser1937Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

THADA
NM_022065.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0840

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:

THADA (HGNC:):

THADA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044373095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THADA	NM_022065.5 linkuse as main transcript	c.5809T>G	p.Ser1937Ala	missense_variant	38/38	ENST00000405975.7	NP_071348.3	Q6YHU6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7 linkuse as main transcript	c.5809T>G	p.Ser1937Ala	missense_variant	38/38	1	NM_022065.5	ENSP00000386088.2		Q6YHU6-1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249050

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135128

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461600

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000263

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.000869

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000290

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.000785

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000497

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2024

The c.5809T>G (p.S1937A) alteration is located in exon 38 (coding exon 37) of the THADA gene. This alteration results from a T to G substitution at nucleotide position 5809, causing the serine (S) at amino acid position 1937 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.2

DANN

Benign

0.89

DEOGEN2

Benign

0.0067

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.25

.;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.013

Sift

Benign

0.87

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.071

MVP

0.014

ClinPred

0.023

GERP RS

1.7

Varity_R

0.038

gMVP

0.17

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