16-15039969-TG-CT

Variant names:

• chr16-15039969-TG-CT
• NM_173474.4:c.638_639delCAinsAG
• NTAN1 p.Pro213Gln

Variant summary

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

The NM_173474.4(NTAN1):​c.638_639delCAinsAG​(p.Pro213Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P213R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NTAN1 NM_173474.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• Publications: 0 publications found

Genes affected

NTAN1 (HGNC:29909): (N-terminal asparagine amidase) The protein encoded by this gene functions in a step-wise process of protein degradation through the N-end rule pathway. This protein acts as a tertiary destabilizing enzyme that deamidates N-terminal L-Asn residues on proteins to produce N-terminal L-Asp. L-Asp substrates are subsequently conjugated to L-Arg, which is recognized by specific E3 ubiquitin ligases and targeted to the proteasome. Pseudogenes of this gene are located on the long arms of chromosomes 8, 10 and 12. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

PDXDC1 (HGNC:28995): (pyridoxal dependent decarboxylase domain containing 1) Enables cadherin binding activity. Predicted to be involved in carboxylic acid metabolic process. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173474.4. 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
	NTAN1	NM_173474.4	MANE Select	c.638_639delCAinsAG	p.Pro213Gln	missense splice_region	N/A	NP_775745.1	Q96AB6
	NTAN1	NM_001270766.2		c.323_324delCAinsAG	p.Pro108Gln	missense splice_region	N/A	NP_001257695.1	A0A087X0T5
	NTAN1	NM_001270767.2		c.323_324delCAinsAG	p.Pro108Gln	missense splice_region	N/A	NP_001257696.1	A0A087X0T5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTAN1	ENST00000287706.8	TSL:1 MANE Select	c.638_639delCAinsAG	p.Pro213Gln	missense splice_region	N/A	ENSP00000287706.3	Q96AB6
	PDXDC1	ENST00000535621.6	TSL:1	c.1399+9913_1399+9914delTGinsCT		intron	N/A	ENSP00000437835.2	Q86XE2
	NTAN1	ENST00000566419.1	TSL:3	c.557_558delCAinsAG	p.Pro186Gln	missense splice_region	N/A	ENSP00000454883.1	H3BNJ5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

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: chr16-15133826;