Variant 1-154544394-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182499.4(TDRD10):c.674C>T(p.Ala225Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 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: 6.9e-7 ( 0 hom. )

Consequence

TDRD10
NM_182499.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.748

Variant links:

Genes affected

TDRD10 (HGNC:25316): (tudor domain containing 10) Predicted to enable RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

TDRD10 links:

TDRD10 (HGNC:):

TDRD10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD10	NM_182499.4 linkuse as main transcript	c.674C>T	p.Ala225Val	missense_variant	10/13	ENST00000368482.8	NP_872305.3	Q5VZ19-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD10	ENST00000368482.8 linkuse as main transcript	c.674C>T	p.Ala225Val	missense_variant	10/13	1	NM_182499.4	ENSP00000357467.4		Q5VZ19-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000471

AC:

AN:

212282

Hom.:

AF XY:

0.00

AC XY:

AN XY:

113584

show subpopulations

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 SAS exome

AF:

0.0000376

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.95e-7

AC:

AN:

1439856

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713800

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:

0.0000121

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

May 06, 2024

The c.674C>T (p.A225V) alteration is located in exon 10 (coding exon 9) of the TDRD10 gene. This alteration results from a C to T substitution at nucleotide position 674, causing the alanine (A) at amino acid position 225 to be replaced by a valine (V). 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

0.086

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

DANN

Benign

0.89

DEOGEN2

Benign

0.00072

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.20

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.0050

Sift

Benign

0.29

T;T

Polyphen

0.0

B;B

Vest4

0.094

MutPred

0.42

Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);

MVP

0.048

MPC

0.38

ClinPred

0.065

GERP RS

-7.3

Varity_R

0.022

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: 10

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