1-151404532-TA-T

Variant names:

• chr1-151404532-TA-T
• rs923196184
• NM_015100.4:c.*269delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_015100.4(POGZ):​c.*269delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 660,890 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (6 hom., cov: 32)
  • Exomes 𝑓: 0.17 (1 hom.)
• Consequence: POGZ NM_015100.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.191
• 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: Labcorp Genetics (formerly Invitae), Illumina, G2P, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-151404532-TA-T is Benign according to our data. Variant chr1-151404532-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1196316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00772 (1094/141790) while in subpopulation AFR AF = 0.0196 (761/38904). AF 95% confidence interval is 0.0184. There are 6 homozygotes in GnomAd4. There are 544 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1094 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POGZ	NM_015100.4	c.*269delT		3_prime_UTR_variant	Exon 19 of 19	ENST00000271715.7	NP_055915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POGZ	ENST00000271715.7	c.*269delT		3_prime_UTR_variant	Exon 19 of 19	1	NM_015100.4	ENSP00000271715.2

Frequencies

GnomAD3 genomes AF: 0.00772 AC: 1094 AN: 141754 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00422

Gnomad ASJ AF: 0.000898

Gnomad EAS AF: 0.00141

Gnomad SAS AF: 0.000887

Gnomad FIN AF: 0.00702

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.00283

Gnomad OTH AF: 0.00982

GnomAD4 exome AF: 0.167 AC: 86513 AN: 519100 Hom.: 1 Cov.: 3 AF XY: 0.167 AC XY: 40727 AN XY: 243964

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.195 AC: 2244 AN: 11512

American (AMR) AF: 0.181 AC: 868 AN: 4804

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 1185 AN: 6456

East Asian (EAS) AF: 0.179 AC: 1865 AN: 10426

South Asian (SAS) AF: 0.171 AC: 1731 AN: 10130

European-Finnish (FIN) AF: 0.169 AC: 1176 AN: 6956

Middle Eastern (MID) AF: 0.205 AC: 280 AN: 1366

European-Non Finnish (NFE) AF: 0.165 AC: 73571 AN: 446738

Other (OTH) AF: 0.173 AC: 3593 AN: 20712

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00772 AC: 1094 AN: 141790 Hom.: 6 Cov.: 32 AF XY: 0.00793 AC XY: 544 AN XY: 68580

African (AFR) AF: 0.0196 AC: 761 AN: 38904

American (AMR) AF: 0.00422 AC: 60 AN: 14226

Ashkenazi Jewish (ASJ) AF: 0.000898 AC: 3 AN: 3342

East Asian (EAS) AF: 0.00141 AC: 7 AN: 4962

South Asian (SAS) AF: 0.000668 AC: 3 AN: 4490

European-Finnish (FIN) AF: 0.00702 AC: 57 AN: 8116

Middle Eastern (MID) AF: 0.00360 AC: 1 AN: 278

European-Non Finnish (NFE) AF: 0.00283 AC: 183 AN: 64636

Other (OTH) AF: 0.00975 AC: 19 AN: 1948

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 12, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.19
Mutation Taster		=100/0	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: rs923196184; hg19: chr1-151377008;