1-151424044-C-A

Variant names:

• chr1-151424044-C-A
• NM_015100.4:c.1428G>T
• POGZ p.Arg476Arg

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015100.4(POGZ):​c.1428G>T​(p.Arg476Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POGZ NM_015100.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• 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: Illumina, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP7: Synonymous conserved (PhyloP=0.122 with no splicing effect.

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.1428G>T	p.Arg476Arg	synonymous	Exon 9 of 19	NP_055915.2
	POGZ	NM_001410860.1		c.1449G>T	p.Arg483Arg	synonymous	Exon 9 of 19	NP_001397789.1	A0A8V8TQ67
	POGZ	NM_001194937.2		c.1401G>T	p.Arg467Arg	synonymous	Exon 9 of 19	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.1428G>T	p.Arg476Arg	synonymous	Exon 9 of 19	ENSP00000271715.2	Q7Z3K3-1
	POGZ	ENST00000392723.6	TSL:1	c.1269G>T	p.Arg423Arg	synonymous	Exon 8 of 18	ENSP00000376484.1	Q7Z3K3-2
	POGZ	ENST00000368863.6	TSL:1	c.1143G>T	p.Arg381Arg	synonymous	Exon 7 of 17	ENSP00000357856.2	Q7Z3K3-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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: chr1-151396520;