8-124508492-ATC-GTT

Variant names:

• chr8-124508492-ATC-GTT
• NM_032026.4:c.496_498delGATinsAAC
• TATDN1 p.Asp166Asn

Variant summary

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

The NM_032026.4(TATDN1):​c.496_498delGATinsAAC​(p.Asp166Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TATDN1 NM_032026.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.13
• Publications: 0 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]

MIR6844 (HGNC:50135): (microRNA 6844) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

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.496_498delGATinsAAC	p.Asp166Asn	missense	N/A	NP_114415.1	Q6P1N9-1
	TATDN1	NM_001317889.1		c.496_498delGATinsAAC	p.Asp166Asn	missense	N/A	NP_001304818.1
	TATDN1	NM_001146160.1		c.355_357delGATinsAAC	p.Asp119Asn	missense	N/A	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.496_498delGATinsAAC	p.Asp166Asn	missense	N/A	ENSP00000276692.6	Q6P1N9-1
	TATDN1	ENST00000519548.5	TSL:1	c.355_357delGATinsAAC	p.Asp119Asn	missense	N/A	ENSP00000428336.1	Q6P1N9-2
	TATDN1	ENST00000523214.5	TSL:1	n.496_498delGATinsAAC		non_coding_transcript_exon	Exon 8 of 13	ENSP00000428609.1	G5EA19

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-125520733;