rs3811409

Variant names:

• chr1-151403108-T-C
• rs3811409
• NM_015100.4:c.*1694A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015100.4(POGZ):​c.*1694A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 524,316 control chromosomes in the GnomAD database, including 1,283 homozygotes. 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: 𝑓 0.064 (615 hom., cov: 33)
  • Exomes 𝑓: 0.053 (668 hom.)
• Consequence: POGZ NM_015100.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 6 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: Labcorp Genetics (formerly Invitae), Illumina, G2P, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POGZ	NM_015100.4	MANE Select	c.*1694A>G		3_prime_UTR	Exon 19 of 19	NP_055915.2
	POGZ	NM_001410860.1		c.*1694A>G		3_prime_UTR	Exon 19 of 19	NP_001397789.1
	POGZ	NM_001194937.2		c.*1694A>G		3_prime_UTR	Exon 19 of 19	NP_001181866.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POGZ	ENST00000271715.7	TSL:1 MANE Select	c.*1694A>G		3_prime_UTR	Exon 19 of 19	ENSP00000271715.2
	POGZ	ENST00000392723.6	TSL:1	c.*1694A>G		3_prime_UTR	Exon 18 of 18	ENSP00000376484.1
	POGZ	ENST00000368863.6	TSL:1	c.*1694A>G		3_prime_UTR	Exon 17 of 17	ENSP00000357856.2

Frequencies

GnomAD3 genomes AF: 0.0645 AC: 9812 AN: 152168 Hom.: 612 Cov.: 33

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.0622

GnomAD4 exome AF: 0.0525 AC: 19538 AN: 372030 Hom.: 668 Cov.: 6 AF XY: 0.0515 AC XY: 9050 AN XY: 175674

African (AFR) AF: 0.0346 AC: 233 AN: 6730

American (AMR) AF: 0.180 AC: 76 AN: 422

Ashkenazi Jewish (ASJ) AF: 0.0142 AC: 32 AN: 2252

East Asian (EAS) AF: 0.308 AC: 466 AN: 1514

South Asian (SAS) AF: 0.110 AC: 796 AN: 7212

European-Finnish (FIN) AF: 0.0634 AC: 35 AN: 552

Middle Eastern (MID) AF: 0.0409 AC: 30 AN: 734

European-Non Finnish (NFE) AF: 0.0505 AC: 17201 AN: 340420

Other (OTH) AF: 0.0549 AC: 669 AN: 12194

GnomAD4 genome AF: 0.0645 AC: 9816 AN: 152286 Hom.: 615 Cov.: 33 AF XY: 0.0669 AC XY: 4980 AN XY: 74466

African (AFR) AF: 0.0409 AC: 1701 AN: 41546

American (AMR) AF: 0.104 AC: 1593 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.310 AC: 1609 AN: 5184

South Asian (SAS) AF: 0.113 AC: 546 AN: 4826

European-Finnish (FIN) AF: 0.0589 AC: 626 AN: 10620

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0519 AC: 3528 AN: 68022

Other (OTH) AF: 0.0606 AC: 128 AN: 2112

Alfa AF: 0.0590 Hom.: 707

Bravo AF: 0.0708

Asia WGS AF: 0.138 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs3811409; hg19: chr1-151375584;