1-212815137-G-A

Variant names:

• chr1-212815137-G-A
• rs147372063
• NM_001042552.3:c.806G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001042552.3(TATDN3):​c.806G>A​(p.Arg269Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000882 in 1,611,680 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (8 hom.)
• Consequence: TATDN3 NM_001042552.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.469
• Publications: 6 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033646524).
• BP6: Variant 1-212815137-G-A is Benign according to our data. Variant chr1-212815137-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2349159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

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.806G>A	p.Arg269Gln	missense	Exon 10 of 10	NP_001036017.1	Q17R31-1
	TATDN3	NM_001146171.2		c.827G>A	p.Arg276Gln	missense	Exon 10 of 10	NP_001139643.1	Q17R31-3
	TATDN3	NM_001042553.3		c.803G>A	p.Arg268Gln	missense	Exon 10 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.806G>A	p.Arg269Gln	missense	Exon 10 of 10	ENSP00000355941.4	Q17R31-1
	TATDN3	ENST00000366973.8	TSL:1	c.803G>A	p.Arg268Gln	missense	Exon 10 of 10	ENSP00000355940.4	Q17R31-2
	TATDN3	ENST00000531963.5	TSL:1	c.*70G>A		3_prime_UTR	Exon 10 of 10	ENSP00000433755.1	Q17R31-5

Frequencies

GnomAD3 genomes AF: 0.000920 AC: 140 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000976 AC: 242 AN: 247954 AF XY: 0.000970

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00137

Gnomad ASJ exome AF: 0.00343

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.000879 AC: 1283 AN: 1459394 Hom.: 8 Cov.: 30 AF XY: 0.000886 AC XY: 643 AN XY: 725972

African (AFR) AF: 0.000270 AC: 9 AN: 33344

American (AMR) AF: 0.00134 AC: 59 AN: 43912

Ashkenazi Jewish (ASJ) AF: 0.00296 AC: 77 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.000490 AC: 42 AN: 85644

European-Finnish (FIN) AF: 0.000356 AC: 19 AN: 53334

Middle Eastern (MID) AF: 0.0108 AC: 62 AN: 5746

European-Non Finnish (NFE) AF: 0.000856 AC: 951 AN: 1111410

Other (OTH) AF: 0.00106 AC: 64 AN: 60314

GnomAD4 genome AF: 0.000913 AC: 139 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.00101 AC XY: 75 AN XY: 74466

African (AFR) AF: 0.000168 AC: 7 AN: 41554

American (AMR) AF: 0.00222 AC: 34 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00115 AC: 78 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00107 Hom.: 0

Bravo AF: 0.000873

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.000848 AC: 103

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00180

EpiControl AF: 0.00190

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.035
DANN	Benign	0.86
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.00099	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.52	N
PhyloP100		-0.47
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.11
Sift	Benign	0.61	T
Sift4G	Benign	0.52	T
Polyphen		0.0010	B
Vest4		0.069
MVP		0.030
MPC		0.18
ClinPred		0.0012	T
GERP RS		-9.4
Varity_R		0.059
gMVP		0.37
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs147372063; hg19: chr1-212988479;