chr1-151404903-T-G

Position:

• chr1-151404903-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_015100.4(POGZ):​c.4132A>C​(p.Thr1378Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: POGZ NM_015100.4 missense
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.278

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), POGZ. . Gene score misZ 3.5062 (greater than the threshold 3.09). Trascript score misZ 4.1346 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.055494905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POGZ	NM_015100.4	c.4132A>C	p.Thr1378Pro	missense_variant	19/19	ENST00000271715.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POGZ	ENST00000271715.7	c.4132A>C	p.Thr1378Pro	missense_variant	19/19	1	NM_015100.4	P3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Autism spectrum disorder Other:1

association, no assertion criteria provided

clinical testing

Center of Medical Genetics, Central South University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.020	.;T;.;.;.;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.85	T;T;T;T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.055	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.;.;.;.
MutationTaster	Benign	0.81	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.34	N;N;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.23	T;T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T;T
Polyphen		0.38	B;B;P;.;.;P
Vest4		0.11
MutPred		0.16		.;Loss of phosphorylation at T1378 (P = 0.0118);.;.;.;.;
MVP		0.54
MPC		0.39
ClinPred		0.14	T
GERP RS		3.9
Varity_R		0.059
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs370498156; hg19: chr1-151377379;