Variant chr14-103955669-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153046.3(TDRD9):c.221T>G(p.Leu74Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,398,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

TDRD9
NM_153046.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.571

Variant links:

Genes affected

TDRD9 (HGNC:20122): (tudor domain containing 9) Predicted to enable RNA binding activity. Involved in spermatogenesis. Located in cytoplasm and nucleus. Implicated in spermatogenic failure 30. [provided by Alliance of Genome Resources, Apr 2022]

TDRD9 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052331567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD9	NM_153046.3 linkuse as main transcript	c.221T>G	p.Leu74Arg	missense_variant	2/36	ENST00000409874.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD9	ENST00000409874.9 linkuse as main transcript	c.221T>G	p.Leu74Arg	missense_variant	2/36	5	NM_153046.3	P1	Q8NDG6-1
TDRD9	ENST00000496087.5 linkuse as main transcript	n.233T>G		non_coding_transcript_exon_variant	3/5	4
TDRD9	ENST00000554571.1 linkuse as main transcript	n.96T>G		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000358

AC:

AN:

1398096

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689526

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:

0.00000371

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.45

M_CAP

Benign

0.0065

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.1

REVEL

Benign

0.037

Sift

Benign

0.13

Sift4G

Benign

0.30

Polyphen

0.0050

Vest4

0.14

MutPred

0.31

Gain of loop (P = 0.0166);

MVP

0.095

MPC

0.31

ClinPred

0.10

GERP RS

1.2

Varity_R

0.14

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over