10-133311762-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145806.4(ZNF511):c.601G>A(p.Gly201Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZNF511 NM_145806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.80

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-PRAP1 (HGNC:):

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]

ACMG classification

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=0.22017938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF511	NM_145806.4	c.601G>A	p.Gly201Arg	missense_variant	5/6	ENST00000361518.10
ZNF511-PRAP1	NM_001396060.1	c.601G>A	p.Gly201Arg	missense_variant	5/9
TUBGCP2	NR_046330.2	n.576C>T		non_coding_transcript_exon_variant	1/18
ZNF511	NR_130127.2	n.572G>A		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF511	ENST00000361518.10	c.601G>A	p.Gly201Arg	missense_variant	5/6	1	NM_145806.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461434 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727000

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

The c.601G>A (p.G201R) alteration is located in exon 5 (coding exon 5) of the ZNF511 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the glycine (G) at amino acid position 201 to be replaced by an arginine (R). 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	0.17
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.068	T;.
Eigen	Benign	0.066
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.26
Sift	Benign	0.083	T;D
Sift4G	Benign	0.14	T;T
Polyphen		0.97	D;.
Vest4		0.28
MutPred		0.21		Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);
MVP		0.59
MPC		0.95
ClinPred		0.72	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.068
gMVP		0.26

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: chr10-135125266;