Variant 6-46688188-C-G 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_001010870.3(TDRD6):c.60C>G(p.Phe20Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,397,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TDRD6
NM_001010870.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0910

Variant links:

Genes affected

TDRD6 (HGNC:21339): (tudor domain containing 6) This gene encodes a tudor domain-containing protein and component of the chromatoid body, a type of ribonucleoprotein granule present in male germ cells. Studies in rodents have demonstrated a role for the encoded protein in spermiogenesis and the nonsense mediated decay (NMD) pathway. This protein is a major autoantigen in human patients with autoimmune polyendocrine syndrome type 1 (APS1). [provided by RefSeq, Oct 2016]

TDRD6 links:

TDRD6 (HGNC:):

TDRD6 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=0.20586595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD6	NM_001010870.3 linkuse as main transcript	c.60C>G	p.Phe20Leu	missense_variant	1/4	ENST00000316081.11	NP_001010870.1	O60522-1
TDRD6	NM_001168359.2 linkuse as main transcript	c.60C>G	p.Phe20Leu	missense_variant	1/3		NP_001161831.1	O60522-2
TDRD6	NR_144468.2 linkuse as main transcript	n.1372+6549C>G		intron_variant
TDRD6-AS1	NR_134643.1 linkuse as main transcript	n.-23G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TDRD6	ENST00000316081.11 linkuse as main transcript	c.60C>G	p.Phe20Leu	missense_variant	1/4	1	NM_001010870.3	ENSP00000346065.5	O60522-1
TDRD6	ENST00000544460.5 linkuse as main transcript	c.60C>G	p.Phe20Leu	missense_variant	1/3	2		ENSP00000443299.1	O60522-2
TDRD6-AS1	ENST00000434329.2 linkuse as main transcript	n.-23G>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1397628

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

691558

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:

0.0000184

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 26, 2023

The c.60C>G (p.F20L) alteration is located in exon 1 (coding exon 1) of the TDRD6 gene. This alteration results from a C to G substitution at nucleotide position 60, causing the phenylalanine (F) at amino acid position 20 to be replaced by a leucine (L). 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

0.97

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

.;T

Eigen

Benign

-0.012

Eigen_PC

Benign

-0.032

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.055

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.17

Sift

Benign

0.29

T;T

Sift4G

Benign

0.084

T;T

Polyphen

0.98

.;D

Vest4

0.37

MutPred

0.69

Loss of catalytic residue at F20 (P = 0.0419);Loss of catalytic residue at F20 (P = 0.0419);

MVP

0.25

MPC

0.044

ClinPred

0.40

GERP RS

2.3

Varity_R

0.084

gMVP

0.45

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