21-29037365-ATG-GTC

Variant names:

• chr21-29037365-ATG-GTC
• NM_006447.3:c.538_540delATGinsGTC
• USP16 p.Met180Val

Variant summary

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

The NM_006447.3(USP16):​c.538_540delATGinsGTC​(p.Met180Val) 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: 33)
• Consequence: USP16 NM_006447.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.993
• Publications: 0 publications found

Genes affected

USP16 (HGNC:12614): (ubiquitin specific peptidase 16) This gene encodes a deubiquitinating enzyme that is phosphorylated at the onset of mitosis and then dephosphorylated at the metaphase/anaphase transition. It can deubiquitinate H2A, one of two major ubiquitinated proteins of chromatin, in vitro and a mutant form of the protein was shown to block cell division. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [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_006447.3. 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
	USP16	NM_006447.3	MANE Select	c.538_540delATGinsGTC	p.Met180Val	missense	N/A	NP_006438.1	Q9Y5T5-1
	USP16	NM_001032410.2		c.538_540delATGinsGTC	p.Met180Val	missense	N/A	NP_001027582.1	Q9Y5T5-1
	USP16	NM_001001992.2		c.535_537delATGinsGTC	p.Met179Val	missense	N/A	NP_001001992.1	Q9Y5T5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP16	ENST00000399976.7	TSL:1 MANE Select	c.538_540delATGinsGTC	p.Met180Val	missense	N/A	ENSP00000382858.2	Q9Y5T5-1
	USP16	ENST00000399975.7	TSL:1	c.535_537delATGinsGTC	p.Met179Val	missense	N/A	ENSP00000382857.3	Q9Y5T5-2
	USP16	ENST00000474835.5	TSL:1	n.706_708delATGinsGTC		non_coding_transcript_exon	Exon 6 of 17

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		0.99

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: chr21-30409686;