GeneBe

rs765254477

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022065.5(THADA):​c.5582G>T​(p.Arg1861Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1861H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

THADA
NM_022065.5 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.84

Publications

0 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]
LINC01126 (HGNC:49275): (long intergenic non-protein coding RNA 1126)

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.044436425).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022065.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
THADA
NM_022065.5
MANE Select
c.5582G>Tp.Arg1861Leu
missense
Exon 38 of 38NP_071348.3
THADA
NM_001083953.2
c.5582G>Tp.Arg1861Leu
missense
Exon 38 of 38NP_001077422.1Q6YHU6-1
THADA
NM_001345925.2
c.5582G>Tp.Arg1861Leu
missense
Exon 39 of 39NP_001332854.1Q6YHU6-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
THADA
ENST00000405975.7
TSL:1 MANE Select
c.5582G>Tp.Arg1861Leu
missense
Exon 38 of 38ENSP00000386088.2Q6YHU6-1
THADA
ENST00000405006.8
TSL:1
c.5582G>Tp.Arg1861Leu
missense
Exon 38 of 38ENSP00000385995.4Q6YHU6-1
THADA
ENST00000855634.1
c.5582G>Tp.Arg1861Leu
missense
Exon 39 of 39ENSP00000525693.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
248634
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
0.052
DANN
Benign
0.95
DEOGEN2
Benign
0.00083
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.044
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.4
L
PhyloP100
-1.8
PrimateAI
Benign
0.19
T
PROVEAN
Benign
-0.59
N
REVEL
Benign
0.021
Sift
Benign
0.40
T
Sift4G
Benign
0.50
T
Polyphen
0.0
B
Vest4
0.12
MutPred
0.30
Loss of disorder (P = 0.0375)
MVP
0.014
ClinPred
0.040
T
GERP RS
-6.5
Varity_R
0.023
gMVP
0.13
Mutation Taster
=97/3
polymorphism

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

Other links and lift over

dbSNP: rs765254477; hg19: chr2-43458367; API