Genetic Variant TDRD5:p.Met60Ile (chr1-179592795-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001199085.3(TDRD5):c.180G>A(p.Met60Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,886 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

TDRD5
NM_001199085.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.41

Publications

0 publications found

Variant links:

Genes affected

TDRD5 (HGNC:20614): (tudor domain containing 5) Predicted to be involved in DNA methylation involved in gamete generation; P granule organization; and spermatid development. Predicted to be located in chromatoid body and pi-body. [provided by Alliance of Genome Resources, Apr 2022]

TDRD5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37737837).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199085.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TDRD5	NM_001199085.3	MANE Select	c.180G>A	p.Met60Ile	missense	Exon 2 of 18	NP_001186014.1	Q8NAT2-1
TDRD5	NM_001199089.3		c.180G>A	p.Met60Ile	missense	Exon 2 of 18	NP_001186018.1	Q8NAT2-1
TDRD5	NM_001199091.2		c.180G>A	p.Met60Ile	missense	Exon 2 of 17	NP_001186020.1	Q8NAT2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TDRD5	ENST00000444136.6	TSL:1 MANE Select	c.180G>A	p.Met60Ile	missense	Exon 2 of 18	ENSP00000406052.1	Q8NAT2-1
TDRD5	ENST00000294848.12	TSL:1	c.180G>A	p.Met60Ile	missense	Exon 2 of 17	ENSP00000294848.8	Q8NAT2-3
TDRD5	ENST00000367614.5	TSL:2	c.180G>A	p.Met60Ile	missense	Exon 2 of 17	ENSP00000356586.1	Q8NAT2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251492

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0096

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

5.4

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.2

REVEL

Benign

0.23

Sift

Uncertain

0.013

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.47

MutPred

0.51

Loss of catalytic residue at M60 (P = 0.0485)

MVP

0.36

MPC

0.77

ClinPred

0.85

GERP RS

5.9

Varity_R

0.68

gMVP

0.73

Mutation Taster

=70/30

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over