10-133308971-C-T

Variant summary

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

The NM_145806.4(ZNF511):c.28C>T(p.Arg10Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000225 in 1,242,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ZNF511
NM_145806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.181

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:):

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30713576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF511	NM_145806.4 linkuse as main transcript	c.28C>T	p.Arg10Cys	missense_variant	1/6	ENST00000361518.10
ZNF511-PRAP1	NM_001396060.1 linkuse as main transcript	c.28C>T	p.Arg10Cys	missense_variant	1/9
ZNF511	NR_130127.2 linkuse as main transcript	n.58C>T		non_coding_transcript_exon_variant	1/6
TUBGCP2	NR_046330.2 linkuse as main transcript	n.718+2649G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF511	ENST00000361518.10 linkuse as main transcript	c.28C>T	p.Arg10Cys	missense_variant	1/6	1	NM_145806.4	P1	Q8NB15-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000238

AC:

AN:

1090728

Hom.:

Cov.:

AF XY:

0.0000233

AC XY:

AN XY:

515386

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000337

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000196

Gnomad4 OTH exome

AF:

0.0000230

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jul 05, 2022

The c.28C>T (p.R10C) alteration is located in exon 1 (coding exon 1) of the ZNF511 gene. This alteration results from a C to T substitution at nucleotide position 28, causing the arginine (R) at amino acid position 10 to be replaced by a cysteine (C). 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

Pathogenic

0.69

BayesDel_addAF

Benign

0.0083

BayesDel_noAF

Benign

-0.23

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.049

T;.

Eigen

Benign

0.068

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.75

T;T

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;.

Vest4

0.31

MutPred

0.46

Gain of catalytic residue at L11 (P = 0.0186);Gain of catalytic residue at L11 (P = 0.0186);

MVP

0.11

MPC

0.49

ClinPred

0.77

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.23

gMVP

0.46

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

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