8-124488684-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032026.4(TATDN1):c.804G>C(p.Glu268Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,318 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TATDN1 NM_032026.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TATDN1	NM_032026.4	c.804G>C	p.Glu268Asp	missense_variant	12/12	ENST00000276692.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TATDN1	ENST00000276692.11	c.804G>C	p.Glu268Asp	missense_variant	12/12	1	NM_032026.4	P1
	ENST00000518639.1	n.175C>G		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448318 Hom.: 0 Cov.: 26 AF XY: 0.00000139 AC XY: 1 AN XY: 721316

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: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.804G>C (p.E268D) alteration is located in exon 12 (coding exon 12) of the TATDN1 gene. This alteration results from a G to C substitution at nucleotide position 804, causing the glutamic acid (E) at amino acid position 268 to be replaced by an aspartic acid (D). 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	0.85
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.078	T;T;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.0060	T
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Benign	-0.46	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.69	T
Sift4G	Uncertain	0.045	D;T;T;T
Polyphen		0.27, 0.93	.;B;.;P
Vest4		0.80
MutPred		0.67		.;.;.;Loss of phosphorylation at S307 (P = 0.3594);
MVP		0.30
MPC		0.026
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.85
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr8-125500925;