rs774499440

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001042552.3(TATDN3):​c.176A>C​(p.Tyr59Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. Y59C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

TATDN3
NM_001042552.3 missense, splice_region

Scores

5
11
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.09
Variant links:
Genes affected
TATDN3 (HGNC:27010): (TatD DNase domain containing 3) 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 nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TATDN3NM_001042552.3 linkc.176A>C p.Tyr59Ser missense_variant, splice_region_variant Exon 4 of 10 ENST00000366974.9 NP_001036017.1 Q17R31-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TATDN3ENST00000366974.9 linkc.176A>C p.Tyr59Ser missense_variant, splice_region_variant Exon 4 of 10 1 NM_001042552.3 ENSP00000355941.4 Q17R31-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461538
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727114
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.23
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.069
.;T;.;.;.;T;T
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.92
D;D;D;D;D;D;D
M_CAP
Benign
0.044
D
MetaRNN
Pathogenic
0.90
D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.10
T
MutationAssessor
Uncertain
2.7
M;M;M;M;M;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Pathogenic
-5.7
D;D;D;D;D;D;D
REVEL
Pathogenic
0.77
Sift
Uncertain
0.010
D;D;D;D;D;D;D
Sift4G
Uncertain
0.042
D;D;T;D;D;D;D
Polyphen
0.98, 0.99
.;D;.;.;D;.;.
Vest4
0.68
MutPred
0.76
Gain of disorder (P = 0.0221);Gain of disorder (P = 0.0221);Gain of disorder (P = 0.0221);Gain of disorder (P = 0.0221);Gain of disorder (P = 0.0221);Gain of disorder (P = 0.0221);.;
MVP
0.33
MPC
0.70
ClinPred
1.0
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.78
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

hg19: chr1-212970456; API