8-124515962-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032026.4(TATDN1):c.271C>T(p.Leu91Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TATDN1 NM_032026.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16566339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TATDN1	NM_032026.4	c.271C>T	p.Leu91Phe	missense_variant	5/12	ENST00000276692.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TATDN1	ENST00000276692.11	c.271C>T	p.Leu91Phe	missense_variant	5/12	1	NM_032026.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jun 07, 2023

The c.271C>T (p.L91F) alteration is located in exon 5 (coding exon 5) of the TATDN1 gene. This alteration results from a C to T substitution at nucleotide position 271, causing the leucine (L) at amino acid position 91 to be replaced by a phenylalanine (F). 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	Benign	0.087
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T;.;.;.;T;T;.
Eigen	Benign	-0.056
Eigen_PC	Benign	-0.0043
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D;D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.91	N;N;N
PrimateAI	Benign	0.23	T
Sift4G	Benign	0.073	T;T;T;T;T;T;T;.
Polyphen		0.0080, 0.17	.;B;.;B;.;.;.;.
Vest4		0.16
MutPred		0.38		.;Gain of helix (P = 0.0325);.;Gain of helix (P = 0.0325);.;Gain of helix (P = 0.0325);.;.;
MVP		0.28
MPC		0.012
ClinPred		0.35	T
GERP RS		2.8
Varity_R		0.22
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1819433985; hg19: chr8-125528203;