Genetic Variant ZNF511:p.Glu153Asp (chr10-133310193-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145806.4(ZNF511):c.459G>T(p.Glu153Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF511
NM_145806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.35

Variant links:

Genes affected

ZNF511 (HGNC:28445): (zinc finger protein 511) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ZNF511 links:

ZNF511-PRAP1 (HGNC:38088): (ZNF511-PRAP1 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ZNF511 (zinc finger protein 511) and PRAP1 (proline-rich acidic protein 1) genes on chromosome 10. The putative readthrough transcript may encode a fusion protein that shares sequence identity with each individual gene product and may be involved in the regulation of gene promoters, particularly those found on transfected plasmids. [provided by RefSeq, Apr 2017]

ZNF511-PRAP1 links:

TUBGCP2 (HGNC:18599): (tubulin gamma complex component 2) Predicted to enable gamma-tubulin binding activity. Predicted to contribute to microtubule minus-end binding activity. Involved in brain development and neuron migration. Located in centrosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TUBGCP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28673947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF511	NM_145806.4 link	c.459G>T	p.Glu153Asp	missense_variant	Exon 4 of 6	ENST00000361518.10	NP_665805.2	Q8NB15-2
ZNF511-PRAP1	NM_001396060.1 link	c.459G>T	p.Glu153Asp	missense_variant	Exon 4 of 9		NP_001382989.1
ZNF511	NR_130127.2 link	n.489G>T		non_coding_transcript_exon_variant	Exon 4 of 6
TUBGCP2	NR_046330.2 link	n.718+1427C>A		intron_variant	Intron 1 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF511	ENST00000361518.10 link	c.459G>T	p.Glu153Asp	missense_variant	Exon 4 of 6	1	NM_145806.4	ENSP00000355251.5		Q8NB15-2
ZNF511-PRAP1	ENST00000368554.8 link	c.285G>T	p.Glu95Asp	missense_variant	Exon 3 of 8	2		ENSP00000357542.5		H7BY64

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.459G>T (p.E153D) alteration is located in exon 4 (coding exon 4) of the ZNF511 gene. This alteration results from a G to T substitution at nucleotide position 459, causing the glutamic acid (E) at amino acid position 153 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

T;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

T;D

M_CAP

Benign

0.0042

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.10

Sift

Benign

0.47

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.68

P;.

Vest4

0.47

MutPred

0.31

Loss of ubiquitination at K156 (P = 0.1151);Loss of ubiquitination at K156 (P = 0.1151);

MVP

0.055

MPC

0.69

ClinPred

0.88

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.076

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over