17-17303723-GC-AT

Variant names:

• chr17-17303723-GC-AT
• NM_020201.4:c.173_174delGCinsAT
• NT5M p.Arg58His

Variant summary

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

The NM_020201.4(NT5M):​c.173_174delGCinsAT​(p.Arg58His) variant causes a missense 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NT5M NM_020201.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• Publications: 0 publications found

Genes affected

NT5M (HGNC:15769): (5',3'-nucleotidase, mitochondrial) This gene encodes a 5' nucleotidase that localizes to the mitochondrial matrix. This enzyme dephosphorylates the 5'- and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020201.4. 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
	NT5M	NM_020201.4	MANE Select	c.173_174delGCinsAT	p.Arg58His	missense	N/A	NP_064586.1	Q9NPB1
	NT5M	NM_001438936.1		c.173_174delGCinsAT	p.Arg58His	missense	N/A	NP_001425865.1
	NT5M	NM_001438937.1		c.173_174delGCinsAT	p.Arg58His	missense	N/A	NP_001425866.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5M	ENST00000389022.9	TSL:1 MANE Select	c.173_174delGCinsAT	p.Arg58His	missense	N/A	ENSP00000373674.4	Q9NPB1
	NT5M	ENST00000616989.1	TSL:1	c.173_174delGCinsAT	p.Arg58His	missense	N/A	ENSP00000481269.1	Q2I378
	NT5M	ENST00000879604.1		c.173_174delGCinsAT	p.Arg58His	missense	N/A	ENSP00000549663.1

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		3.0

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: chr17-17207037;