Variant 13-60494518-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001146070.2(TDRD3):c.801A>T(p.Leu267Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TDRD3
NM_001146070.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

TDRD3 (HGNC:20612): (tudor domain containing 3) Enables chromatin binding activity; methylated histone binding activity; and transcription coactivator activity. Predicted to be involved in chromatin organization and positive regulation of transcription, DNA-templated. Located in Golgi apparatus; cytosol; and nucleoplasm. Colocalizes with exon-exon junction complex. [provided by Alliance of Genome Resources, Apr 2022]

TDRD3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08289915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD3	NM_001146070.2 linkuse as main transcript	c.801A>T	p.Leu267Phe	missense_variant	8/14	ENST00000377881.8	NP_001139542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD3	ENST00000377881.8 linkuse as main transcript	c.801A>T	p.Leu267Phe	missense_variant	8/14	1	NM_001146070.2	ENSP00000367113	P1	Q9H7E2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461524

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Jun 11, 2024

The c.801A>T (p.L267F) alteration is located in exon 8 (coding exon 8) of the TDRD3 gene. This alteration results from a A to T substitution at nucleotide position 801, causing the leucine (L) at amino acid position 267 to be replaced by a phenylalanine (F). 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

0.053

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0034

T;T;.;T;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.79

T;.;T;.;.;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.083

T;T;T;T;T;T

MetaSVM

Benign

-0.41

MutationAssessor

Benign

-0.090

N;N;.;N;N;.

MutationTaster

Benign

0.73

D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

0.96

N;N;N;N;.;.

REVEL

Benign

0.18

Sift

Benign

0.67

T;T;T;T;.;.

Sift4G

Benign

1.0

T;T;T;T;.;T

Polyphen

0.0

B;B;B;B;B;B

Vest4

0.11

MutPred

0.27

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;

MVP

0.82

MPC

0.17

ClinPred

0.59

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.088

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