Variant 1-36286541-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005119.4(THRAP3):c.311A>G(p.Tyr104Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,888 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: 0.0000014 ( 0 hom. )

Consequence

THRAP3
NM_005119.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.58

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3924083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THRAP3	NM_005119.4 linkuse as main transcript	c.311A>G	p.Tyr104Cys	missense_variant	4/12	ENST00000354618.10	NP_005110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
THRAP3	ENST00000354618.10 linkuse as main transcript	c.311A>G	p.Tyr104Cys	missense_variant	4/12	1	NM_005119.4	ENSP00000346634	P2
THRAP3	ENST00000469141.6 linkuse as main transcript	c.311A>G	p.Tyr104Cys	missense_variant	5/13	1		ENSP00000433825	P2
THRAP3	ENST00000648638.1 linkuse as main transcript	c.311A>G	p.Tyr104Cys	missense_variant	5/14			ENSP00000498001	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 15, 2022

The c.311A>G (p.Y104C) alteration is located in exon 4 (coding exon 2) of the THRAP3 gene. This alteration results from a A to G substitution at nucleotide position 311, causing the tyrosine (Y) at amino acid position 104 to be replaced by a cysteine (C). 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

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.42

T;T;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

.;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-2.3

N;N;.

REVEL

Benign

0.18

Sift

Uncertain

0.0020

D;D;.

Sift4G

Benign

0.14

T;T;.

Polyphen

1.0

D;D;.

Vest4

0.70

MutPred

0.25

Loss of phosphorylation at Y104 (P = 0.1225);Loss of phosphorylation at Y104 (P = 0.1225);Loss of phosphorylation at Y104 (P = 0.1225);

MVP

0.17

MPC

0.55

ClinPred

0.88

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.72

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over