chr1-151404772-T-C

Variant names:

• chr1-151404772-T-C
• rs6667714
• NM_015100.4:c.*30A>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.*30A>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 0.996 in 1,549,416 control chromosomes in the GnomAD database, including 768,065 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 0.98 (71704 hom., cov: 23)
  • Exomes 𝑓: 1.0 (696361 hom.)
• Consequence: POGZ NM_015100.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.393
• Publications: 7 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POGZ	NM_015100.4	c.*30A>G		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.*30A>G		3_prime_UTR_variant	Exon 19 of 19	1	NM_015100.4	ENSP00000271715.2

Frequencies

GnomAD3 genomes AF: 0.976 AC: 146585 AN: 150202 Hom.: 71652 Cov.: 23

Gnomad AFR AF: 0.914

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.988

GnomAD2 exomes AF: 0.993 AC: 205259 AN: 206734 AF XY: 0.995

Gnomad AFR exome AF: 0.911

Gnomad AMR exome AF: 0.996

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.998

GnomAD4 exome AF: 0.998 AC: 1395765 AN: 1399096 Hom.: 696361 Cov.: 37 AF XY: 0.998 AC XY: 687241 AN XY: 688678

African (AFR) AF: 0.912 AC: 28821 AN: 31604

American (AMR) AF: 0.996 AC: 36332 AN: 36470

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 22174 AN: 22174

East Asian (EAS) AF: 1.00 AC: 39030 AN: 39030

South Asian (SAS) AF: 1.00 AC: 76326 AN: 76348

European-Finnish (FIN) AF: 1.00 AC: 50827 AN: 50830

Middle Eastern (MID) AF: 0.997 AC: 5402 AN: 5416

European-Non Finnish (NFE) AF: 1.00 AC: 1079603 AN: 1079678

Other (OTH) AF: 0.995 AC: 57250 AN: 57546

GnomAD4 genome AF: 0.976 AC: 146696 AN: 150320 Hom.: 71704 Cov.: 23 AF XY: 0.977 AC XY: 71619 AN XY: 73310

African (AFR) AF: 0.914 AC: 37029 AN: 40518

American (AMR) AF: 0.994 AC: 14995 AN: 15090

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3470 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5014 AN: 5014

South Asian (SAS) AF: 1.00 AC: 4717 AN: 4718

European-Finnish (FIN) AF: 1.00 AC: 10376 AN: 10376

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67826 AN: 67840

Other (OTH) AF: 0.988 AC: 2063 AN: 2088

Alfa AF: 0.992 Hom.: 16306

Bravo AF: 0.972

Asia WGS AF: 0.996 AC: 3463 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.6
DANN	Benign	0.83
PhyloP100		-0.39
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: rs6667714; hg19: chr1-151377248;