chr8-124515920-C-T

Variant names:

• chr8-124515920-C-T
• rs201105584
• NM_032026.4:c.313G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032026.4(TATDN1):​c.313G>A​(p.Gly105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000059 (0 hom.)
• Consequence: TATDN1 NM_032026.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.32
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18043542).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032026.4. 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
	TATDN1	NM_032026.4	MANE Select	c.313G>A	p.Gly105Arg	missense	Exon 5 of 12	NP_114415.1	Q6P1N9-1
	TATDN1	NM_001317889.1		c.313G>A	p.Gly105Arg	missense	Exon 5 of 13	NP_001304818.1
	TATDN1	NM_001146160.1		c.172G>A	p.Gly58Arg	missense	Exon 3 of 10	NP_001139632.1	Q6P1N9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TATDN1	ENST00000276692.11	TSL:1 MANE Select	c.313G>A	p.Gly105Arg	missense	Exon 5 of 12	ENSP00000276692.6	Q6P1N9-1
	TATDN1	ENST00000519548.5	TSL:1	c.172G>A	p.Gly58Arg	missense	Exon 3 of 10	ENSP00000428336.1	Q6P1N9-2
	TATDN1	ENST00000523214.5	TSL:1	n.313G>A		non_coding_transcript_exon	Exon 5 of 13	ENSP00000428609.1	G5EA19

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251388 AF XY: 0.0000662

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000588 AC: 86 AN: 1461732 Hom.: 0 Cov.: 31 AF XY: 0.0000605 AC XY: 44 AN XY: 727156

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.0000755 AC: 84 AN: 1111958

Other (OTH) AF: 0.0000331 AC: 2 AN: 60388

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000871 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.25
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Benign	0.079	T
Sift4G	Benign	0.17	T
Polyphen		0.044	B
Vest4		0.28
MutPred		0.55		Gain of solvent accessibility (P = 0.0097)
MVP		0.30
MPC		0.012
ClinPred		0.12	T
GERP RS		5.6
Varity_R		0.20
gMVP		0.67
Mutation Taster		=59/41	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: rs201105584; hg19: chr8-125528161;