1-151406445-G-T

Variant names:

• chr1-151406445-G-T
• rs756659230
• NM_015100.4:c.2590C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015100.4(POGZ):​c.2590C>A​(p.Arg864Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000715 in 1,397,828 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: POGZ NM_015100.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.84
• Publications: 1 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, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).

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.2590C>A	p.Arg864Arg	synonymous	Exon 19 of 19	NP_055915.2
	POGZ	NM_001410860.1		c.2611C>A	p.Arg871Arg	synonymous	Exon 19 of 19	NP_001397789.1	A0A8V8TQ67
	POGZ	NM_001194937.2		c.2563C>A	p.Arg855Arg	synonymous	Exon 19 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.2590C>A	p.Arg864Arg	synonymous	Exon 19 of 19	ENSP00000271715.2	Q7Z3K3-1
	POGZ	ENST00000392723.6	TSL:1	c.2431C>A	p.Arg811Arg	synonymous	Exon 18 of 18	ENSP00000376484.1	Q7Z3K3-2
	POGZ	ENST00000368863.6	TSL:1	c.2305C>A	p.Arg769Arg	synonymous	Exon 17 of 17	ENSP00000357856.2	Q7Z3K3-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000507 AC: 1 AN: 197430 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397828 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 689432

African (AFR) AF: 0.00 AC: 0 AN: 31142

American (AMR) AF: 0.00 AC: 0 AN: 34134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21556

East Asian (EAS) AF: 0.00 AC: 0 AN: 39272

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 74918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5436

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082998

Other (OTH) AF: 0.00 AC: 0 AN: 57582

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	9.9
DANN	Benign	0.84
PhyloP100		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs756659230; hg19: chr1-151378921;