rs774499440

Variant names:

• chr1-212797114-A-C
• rs774499440
• NM_001042552.3:c.176A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-212797114-A-C
• chr1-212797114-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_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 𝑓: 6.8e-7 (0 hom.)
• Consequence: TATDN3 NM_001042552.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.09
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042552.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TATDN3	NM_001042552.3	MANE Select	c.176A>C	p.Tyr59Ser	missense splice_region	Exon 4 of 10	NP_001036017.1	Q17R31-1
	TATDN3	NM_001146171.2		c.176A>C	p.Tyr59Ser	missense splice_region	Exon 4 of 10	NP_001139643.1	Q17R31-3
	TATDN3	NM_001042553.3		c.176A>C	p.Tyr59Ser	missense splice_region	Exon 4 of 10	NP_001036018.1	Q17R31-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TATDN3	ENST00000366974.9	TSL:1 MANE Select	c.176A>C	p.Tyr59Ser	missense splice_region	Exon 4 of 10	ENSP00000355941.4	Q17R31-1
	TATDN3	ENST00000366973.8	TSL:1	c.176A>C	p.Tyr59Ser	missense splice_region	Exon 4 of 10	ENSP00000355940.4	Q17R31-2
	TATDN3	ENST00000531963.5	TSL:1	c.176A>C	p.Tyr59Ser	missense splice_region	Exon 4 of 10	ENSP00000433755.1	Q17R31-5

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

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111708

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.042	D
Polyphen		0.98	D
Vest4		0.68
MutPred		0.76		Gain of disorder (P = 0.0221)
MVP		0.33
MPC		0.70
ClinPred		1.0	D
GERP RS		5.7
PromoterAI		0.0085	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.78
gMVP		0.93
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs774499440; hg19: chr1-212970456;