rs1571294

Variant names:

• chr1-151404931-A-C
• rs1571294
• NM_015100.4:c.4104T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-151404931-A-C
• chr1-151404931-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015100.4(POGZ):​c.4104T>G​(p.Thr1368Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 1,614,044 control chromosomes in the GnomAD database, including 11,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1368T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.12 (2360 hom., cov: 32)
  • Exomes 𝑓: 0.041 (8997 hom.)
• Consequence: POGZ NM_015100.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.515
• Publications: 16 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Illumina

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-151404931-A-C is Benign according to our data. Variant chr1-151404931-A-C is described in ClinVar as Benign. ClinVar VariationId is 587824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.515 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POGZ	NM_015100.4	MANE Select	c.4104T>G	p.Thr1368Thr	synonymous	Exon 19 of 19	NP_055915.2
	POGZ	NM_001410860.1		c.4125T>G	p.Thr1375Thr	synonymous	Exon 19 of 19	NP_001397789.1	A0A8V8TQ67
	POGZ	NM_001194937.2		c.4077T>G	p.Thr1359Thr	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.4104T>G	p.Thr1368Thr	synonymous	Exon 19 of 19	ENSP00000271715.2	Q7Z3K3-1
	POGZ	ENST00000392723.6	TSL:1	c.3945T>G	p.Thr1315Thr	synonymous	Exon 18 of 18	ENSP00000376484.1	Q7Z3K3-2
	POGZ	ENST00000368863.6	TSL:1	c.3819T>G	p.Thr1273Thr	synonymous	Exon 17 of 17	ENSP00000357856.2	Q7Z3K3-5

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17942 AN: 152036 Hom.: 2351 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00413

Gnomad OTH AF: 0.0932

GnomAD2 exomes AF: 0.114 AC: 28715 AN: 251466 AF XY: 0.0999

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.0105

Gnomad EAS exome AF: 0.411

Gnomad FIN exome AF: 0.0698

Gnomad NFE exome AF: 0.00485

Gnomad OTH exome AF: 0.0789

GnomAD4 exome AF: 0.0408 AC: 59714 AN: 1461890 Hom.: 8997 Cov.: 36 AF XY: 0.0402 AC XY: 29258 AN XY: 727248

African (AFR) AF: 0.269 AC: 9006 AN: 33480

American (AMR) AF: 0.316 AC: 14143 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00945 AC: 247 AN: 26136

East Asian (EAS) AF: 0.456 AC: 18100 AN: 39700

South Asian (SAS) AF: 0.0895 AC: 7718 AN: 86258

European-Finnish (FIN) AF: 0.0647 AC: 3457 AN: 53420

Middle Eastern (MID) AF: 0.0270 AC: 156 AN: 5768

European-Non Finnish (NFE) AF: 0.00255 AC: 2840 AN: 1112008

Other (OTH) AF: 0.0670 AC: 4047 AN: 60396

GnomAD4 genome AF: 0.118 AC: 17989 AN: 152154 Hom.: 2360 Cov.: 32 AF XY: 0.125 AC XY: 9272 AN XY: 74382

African (AFR) AF: 0.251 AC: 10427 AN: 41468

American (AMR) AF: 0.224 AC: 3419 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.442 AC: 2284 AN: 5162

South Asian (SAS) AF: 0.111 AC: 535 AN: 4824

European-Finnish (FIN) AF: 0.0759 AC: 805 AN: 10604

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00415 AC: 282 AN: 68022

Other (OTH) AF: 0.0960 AC: 203 AN: 2114

Alfa AF: 0.0432 Hom.: 1262

Bravo AF: 0.137

Asia WGS AF: 0.282 AC: 979 AN: 3478

EpiCase AF: 0.00393

EpiControl AF: 0.00439

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
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: rs1571294; hg19: chr1-151377407; COSMIC: COSV51851285; COSMIC: COSV51851285;