Variant 1-36289239-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The ENST00000354618.10(THRAP3):c.1220A>G(p.Gln407Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

THRAP3
ENST00000354618.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26

Variant links:

Genes affected

THRAP3 (HGNC:22964): (thyroid hormone receptor associated protein 3) Enables phosphoprotein binding activity; thyroid hormone receptor binding activity; and transcription coactivator activity. Involved in nuclear-transcribed mRNA catabolic process; positive regulation of circadian rhythm; and regulation of RNA metabolic process. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in nuclear speck. Part of mediator complex. Colocalizes with exon-exon junction complex. [provided by Alliance of Genome Resources, Apr 2022]

THRAP3 links:

THRAP3 (HGNC:):

THRAP3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18312666).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THRAP3	NM_005119.4 linkuse as main transcript	c.1220A>G	p.Gln407Arg	missense_variant	5/12	ENST00000354618.10	NP_005110.2	Q9Y2W1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
THRAP3	ENST00000354618.10 linkuse as main transcript	c.1220A>G	p.Gln407Arg	missense_variant	5/12	1	NM_005119.4	ENSP00000346634.5	Q9Y2W1
THRAP3	ENST00000469141.6 linkuse as main transcript	c.1220A>G	p.Gln407Arg	missense_variant	6/13	1		ENSP00000433825.1	Q9Y2W1
THRAP3	ENST00000648638.1 linkuse as main transcript	c.1220A>G	p.Gln407Arg	missense_variant	6/14			ENSP00000498001.1	A0A3B3ITZ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251218

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

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:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Jan 04, 2022

The c.1220A>G (p.Q407R) alteration is located in exon 5 (coding exon 3) of the THRAP3 gene. This alteration results from a A to G substitution at nucleotide position 1220, causing the glutamine (Q) at amino acid position 407 to be replaced by an arginine (R). 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

0.33

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

.;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.91

N;N;.

REVEL

Benign

0.15

Sift

Uncertain

0.0020

D;D;.

Sift4G

Benign

0.41

T;T;.

Polyphen

0.99

D;D;.

Vest4

0.60

MutPred

0.16

Gain of MoRF binding (P = 0.0243);Gain of MoRF binding (P = 0.0243);Gain of MoRF binding (P = 0.0243);

MVP

0.26

MPC

1.3

ClinPred

0.44

GERP RS

6.0

Varity_R

0.36

gMVP

0.068

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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