chr10-133308962-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145806.4(ZNF511):c.19C>A(p.Leu7Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000434 in 1,240,250 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00042 ( 1 hom. )

Consequence

ZNF511
NM_145806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.179

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Norman-Roberts syndrome
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

TUBGCP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045891106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF511	NM_145806.4 link	c.19C>A	p.Leu7Met	missense_variant	Exon 1 of 6	ENST00000361518.10	NP_665805.2	Q8NB15-2
TUBGCP2	NM_006659.4 link	c.-179G>T		upstream_gene_variant		ENST00000252936.8	NP_006650.1	Q9BSJ2-1Q53EQ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF511	ENST00000361518.10 link	c.19C>A	p.Leu7Met	missense_variant	Exon 1 of 6	1	NM_145806.4	ENSP00000355251.5		Q8NB15-2
TUBGCP2	ENST00000252936.8 link	c.-179G>T		upstream_gene_variant		2	NM_006659.4	ENSP00000252936.3		Q9BSJ2-1

Frequencies

GnomAD3 genomes

AF:

0.000520

AC:

AN:

151874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000722

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.000595

AC:

AN:

8398

AF XY:

0.000979

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000254

Gnomad NFE exome

AF:

0.00718

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000422

AC:

459

AN:

1088268

Hom.:

Cov.:

AF XY:

0.000453

AC XY:

233

AN XY:

514238

show subpopulations

African (AFR)

AF:

0.0000442

AC:

AN:

22610

American (AMR)

AF:

0.000245

AC:

AN:

8172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13998

East Asian (EAS)

AF:

0.00

AC:

AN:

25992

South Asian (SAS)

AF:

0.00411

AC:

AN:

20662

European-Finnish (FIN)

AF:

0.000239

AC:

AN:

33440

Middle Eastern (MID)

AF:

0.00207

AC:

AN:

2896

European-Non Finnish (NFE)

AF:

0.000362

AC:

332

AN:

917222

Other (OTH)

AF:

0.000578

AC:

AN:

43276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000520

AC:

AN:

151982

Hom.:

Cov.:

AF XY:

0.000713

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41540

American (AMR)

AF:

0.000393

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00393

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000190

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000722

AC:

AN:

67892

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000324

Hom.:

Bravo

AF:

0.000378

ExAC

AF:

0.000150

AC:

Asia WGS

AF:

0.000580

AC:

AN:

3458

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.19C>A (p.L7M) alteration is located in exon 1 (coding exon 1) of the ZNF511 gene. This alteration results from a C to A substitution at nucleotide position 19, causing the leucine (L) at amino acid position 7 to be replaced by a methionine (M). 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

0.33

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.52

T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

M;M

PhyloP100

-0.18

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.60

N;N

REVEL

Benign

0.083

Sift

Benign

0.052

T;D

Sift4G

Uncertain

0.034

D;D

Polyphen

0.75

P;.

Vest4

0.40

MutPred

0.32

Gain of catalytic residue at L7 (P = 0.0722);Gain of catalytic residue at L7 (P = 0.0722);

MVP

0.030

MPC

0.35

ClinPred

0.061

GERP RS

-0.64

PromoterAI

0.0038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.086

gMVP

0.32

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr10-133308962-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over