10-133308952-G-T

Position:

chr10-133308952-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145806.4(ZNF511):c.9G>T(p.Leu3Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,233,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000046 ( 0 hom. )

Consequence

ZNF511
NM_145806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0870

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2179173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF511	NM_145806.4 link	c.9G>T	p.Leu3Phe	missense_variant	1/6	ENST00000361518.10	NP_665805.2	Q8NB15-2
ZNF511-PRAP1	NM_001396060.1 link	c.9G>T	p.Leu3Phe	missense_variant	1/9		NP_001382989.1
ZNF511	NR_130127.2 link	n.39G>T		non_coding_transcript_exon_variant	1/6
TUBGCP2	NR_046330.2 link	n.718+2668C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF511	ENST00000361518.10 link	c.9G>T	p.Leu3Phe	missense_variant	1/6	1	NM_145806.4	ENSP00000355251.5		Q8NB15-2

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000462

AC:

AN:

1081830

Hom.:

Cov.:

AF XY:

0.00000587

AC XY:

AN XY:

510938

show subpopulations

Gnomad4 AFR exome

AF:

0.0000444

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000328

Gnomad4 OTH exome

AF:

0.0000233

GnomAD4 genome

AF:

0.0000593

AC:

AN:

151768

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 06, 2024

The c.9G>T (p.L3F) alteration is located in exon 1 (coding exon 1) of the ZNF511 gene. This alteration results from a G to T substitution at nucleotide position 9, causing the leucine (L) at amino acid position 3 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.8

DANN

Benign

0.90

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.53

T;T

M_CAP

Pathogenic

0.73

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.10

Sift

Benign

0.036

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.23

MutPred

0.28

Loss of glycosylation at P5 (P = 0.1591);Loss of glycosylation at P5 (P = 0.1591);

MVP

0.030

MPC

0.39

ClinPred

0.23

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.041

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over