chr8-124488610-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_032026.4(TATDN1):c.878T>C(p.Phe293Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,554,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TATDN1
NM_032026.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33

Publications

0 publications found

Variant links:

Genes affected

TATDN1 (HGNC:24220): (TatD DNase domain containing 1) Predicted to enable 3'-5'-exodeoxyribonuclease activity. Predicted to be involved in DNA metabolic process and nucleic acid phosphodiester bond hydrolysis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TATDN1 links:

RNF139 (HGNC:17023): (ring finger protein 139) The protein encoded by this gene is a multi-membrane spanning protein containing a RING-H2 finger. This protein is located in the endoplasmic reticulum, and has been shown to possess ubiquitin ligase activity. This gene was found to be interrupted by a t(3:8) translocation in a family with hereditary renal and non-medulary thyroid cancer. Studies of the Drosophila counterpart suggested that this protein may interact with tumor suppressor protein VHL, as well as with COPS5/JAB1, a protein responsible for the degradation of tumor suppressor CDKN1B/P27KIP. [provided by RefSeq, Jul 2008]

RNF139 Gene-Disease associations (from GenCC):

nonpapillary renal cell carcinoma
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

RNF139 links:

ENSG00000253106 (HGNC:):

ENSG00000253106 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PP3

MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TATDN1	NM_032026.4 link	c.878T>C	p.Phe293Ser	missense_variant	Exon 12 of 12	ENST00000276692.11	NP_114415.1	Q6P1N9-1
RNF139	NM_007218.4 link	c.*966A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000303545.4	NP_009149.2	Q8WU17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TATDN1	ENST00000276692.11 link	c.878T>C	p.Phe293Ser	missense_variant	Exon 12 of 12	1	NM_032026.4	ENSP00000276692.6		Q6P1N9-1
RNF139	ENST00000303545.4 link	c.*966A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_007218.4	ENSP00000304051.4		Q8WU17

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000785

AC:

AN:

242172

AF XY:

0.0000611

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000285

AC:

AN:

1402356

Hom.:

Cov.:

AF XY:

0.0000243

AC XY:

AN XY:

700210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32150

American (AMR)

AF:

0.000118

AC:

AN:

42220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25614

East Asian (EAS)

AF:

0.00

AC:

AN:

39178

South Asian (SAS)

AF:

0.00

AC:

AN:

81580

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.000378

AC:

AN:

5298

European-Non Finnish (NFE)

AF:

0.0000291

AC:

AN:

1064694

Other (OTH)

AF:

0.0000343

AC:

AN:

58314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41444

American (AMR)

AF:

0.000523

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000742

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 08, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.878T>C (p.F293S) alteration is located in exon 12 (coding exon 12) of the TATDN1 gene. This alteration results from a T to C substitution at nucleotide position 878, causing the phenylalanine (F) at amino acid position 293 to be replaced by a serine (S). 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

0.95

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T;.

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.078

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Uncertain

0.43

MutationAssessor

Pathogenic

4.6

.;H;.

PhyloP100

6.3

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-7.0

.;D;D

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

.;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.74

MVP

0.47

MPC

0.080

ClinPred

1.0

GERP RS

4.3

Varity_R

0.99

gMVP

0.82

Mutation Taster

=11/89

disease causing

(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.

chr8-124488610-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over