Genetic Variant TATDN2:p.Pro358Leu (chr3-10270255-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014760.4(TATDN2):c.1073C>T(p.Pro358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,958 control chromosomes in the GnomAD database, including 12,145 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P358S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.15 ( 2110 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10035 hom. )

Consequence

TATDN2
NM_014760.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.966

Publications

23 publications found

Variant links:

Genes affected

TATDN2 (HGNC:28988): (TatD DNase domain containing 2) Predicted to enable metal ion binding activity and nuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TATDN2 links:

ENSG00000272410 (HGNC:):

ENSG00000272410 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004538268).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TATDN2	NM_014760.4 link	c.1073C>T	p.Pro358Leu	missense_variant	Exon 4 of 8	ENST00000448281.7	NP_055575.3	Q93075A0A024R2F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TATDN2	ENST00000448281.7 link	c.1073C>T	p.Pro358Leu	missense_variant	Exon 4 of 8	1	NM_014760.4	ENSP00000408736.2		Q93075
ENSG00000272410	ENST00000437082.5 link	n.902C>T		non_coding_transcript_exon_variant	Exon 3 of 8	2		ENSP00000402783.1		H7C1W4

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22845

AN:

151960

Hom.:

2099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0976

Gnomad OTH

AF:

0.136

GnomAD2 exomes

AF:

0.123

AC:

30912

AN:

251446

AF XY:

0.121

show subpopulations

Gnomad AFR exome

AF:

0.253

Gnomad AMR exome

AF:

0.0641

Gnomad ASJ exome

AF:

0.155

Gnomad EAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.0973

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.108

AC:

157652

AN:

1461880

Hom.:

10035

Cov.:

AF XY:

0.108

AC XY:

78492

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.252

AC:

8431

AN:

33480

American (AMR)

AF:

0.0695

AC:

3109

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

4095

AN:

26134

East Asian (EAS)

AF:

0.279

AC:

11079

AN:

39700

South Asian (SAS)

AF:

0.114

AC:

9820

AN:

86258

European-Finnish (FIN)

AF:

0.131

AC:

7023

AN:

53410

Middle Eastern (MID)

AF:

0.125

AC:

723

AN:

5768

European-Non Finnish (NFE)

AF:

0.0952

AC:

105871

AN:

1112010

Other (OTH)

AF:

0.124

AC:

7501

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

9847

19694

29540

39387

49234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4122

8244

12366

16488

20610

<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

AF:

0.150

AC:

22877

AN:

152078

Hom.:

2110

Cov.:

AF XY:

0.152

AC XY:

11294

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.247

AC:

10258

AN:

41456

American (AMR)

AF:

0.106

AC:

1615

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

510

AN:

3460

East Asian (EAS)

AF:

0.271

AC:

1395

AN:

5156

South Asian (SAS)

AF:

0.120

AC:

576

AN:

4808

European-Finnish (FIN)

AF:

0.144

AC:

1525

AN:

10604

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0976

AC:

6637

AN:

68004

Other (OTH)

AF:

0.136

AC:

288

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

944

1887

2831

3774

4718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.115

Hom.:

3475

Bravo

AF:

0.150

TwinsUK

AF:

0.102

AC:

379

ALSPAC

AF:

0.0947

AC:

365

ESP6500AA

AF:

0.246

AC:

1083

ESP6500EA

AF:

0.0957

AC:

823

ExAC

AF:

0.125

AC:

15211

Asia WGS

AF:

0.186

AC:

649

AN:

3478

EpiCase

AF:

0.0960

EpiControl

AF:

0.103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0025

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.55

.;T

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

0.97

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.079

Sift

Benign

0.037

D;D

Sift4G

Benign

0.28

T;T

Polyphen

0.15

B;B

Vest4

0.052

MPC

0.19

ClinPred

0.036

GERP RS

4.7

Varity_R

0.051

gMVP

0.17

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over