NM_015100.4:c.1895_1896delATinsTC

Variant names:

• chr1-151411655-AT-GA
• NM_015100.4:c.1895_1896delATinsTC
• POGZ p.Asn632Ile

Variant summary

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

The NM_015100.4(POGZ):​c.1895_1896delATinsTC​(p.Asn632Ile) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N632S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POGZ NM_015100.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

POGZ (HGNC:18801): (pogo transposable element derived with ZNF domain) The protein encoded by this gene appears to be a zinc finger protein containing a transposase domain at the C-terminus. This protein was found to interact with the transcription factor SP1 in a yeast two-hybrid system. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Aug 2010]

POGZ Gene-Disease associations (from GenCC):

• intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Illumina

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015100.4. 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
	POGZ	NM_015100.4	MANE Select	c.1895_1896delATinsTC	p.Asn632Ile	missense	N/A	NP_055915.2
	POGZ	NM_001410860.1		c.1916_1917delATinsTC	p.Asn639Ile	missense	N/A	NP_001397789.1	A0A8V8TQ67
	POGZ	NM_001194937.2		c.1868_1869delATinsTC	p.Asn623Ile	missense	N/A	NP_001181866.1	Q7Z3K3-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POGZ	ENST00000271715.7	TSL:1 MANE Select	c.1895_1896delATinsTC	p.Asn632Ile	missense	N/A	ENSP00000271715.2	Q7Z3K3-1
	POGZ	ENST00000392723.6	TSL:1	c.1736_1737delATinsTC	p.Asn579Ile	missense	N/A	ENSP00000376484.1	Q7Z3K3-2
	POGZ	ENST00000368863.6	TSL:1	c.1610_1611delATinsTC	p.Asn537Ile	missense	N/A	ENSP00000357856.2	Q7Z3K3-5

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		1.1

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: chr1-151384131;