1-151404816-G-T

Position:

• chr1-151404816-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Moderate BP6_Moderate

The NM_015100.4(POGZ):​c.4219C>A​(p.Leu1407Met) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POGZ NM_015100.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.13

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=0.17121786).
• BP6: Variant 1-151404816-G-T is Benign according to our data. Variant chr1-151404816-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2581038.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POGZ	NM_015100.4	c.4219C>A	p.Leu1407Met	missense_variant	19/19	ENST00000271715.7	NP_055915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POGZ	ENST00000271715.7	c.4219C>A	p.Leu1407Met	missense_variant	19/19	1	NM_015100.4	ENSP00000271715	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely benign, criteria provided, single submitter

clinical testing

Dr. med. U. Finckh, Human Genetics, Eurofins MVZ

Aug 17, 2023

PM2_SUP, BS2, BP4_MOD (based on REVEL score interpretation of PMID 36413997) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	.;T;.;.;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;N;.;.;.;.
MutationTaster	Benign	0.96	N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.36	N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0080	D;D;D;D;D;D
Sift4G	Benign	0.21	T;T;T;T;T;T
Polyphen		1.0	D;D;D;.;.;D
Vest4		0.25
MutPred		0.14		.;Loss of helix (P = 0.1299);.;.;.;.;
MVP		0.38
MPC		0.64
ClinPred		0.53	D
GERP RS		3.4
Varity_R		0.099
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-151377292;