10-133309411-C-G

Variant names:

• chr10-133309411-C-G
• NM_145806.4:c.175C>G

Variant summary

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

The NM_145806.4(ZNF511):​c.175C>G​(p.Leu59Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF511 NM_145806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.549

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: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]

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF511	NM_145806.4	c.175C>G	p.Leu59Val	missense_variant	Exon 2 of 6	ENST00000361518.10	NP_665805.2
ZNF511-PRAP1	NM_001396060.1	c.175C>G	p.Leu59Val	missense_variant	Exon 2 of 9		NP_001382989.1
ZNF511	NR_130127.2	n.205C>G		non_coding_transcript_exon_variant	Exon 2 of 6
TUBGCP2	NR_046330.2	n.718+2209G>C		intron_variant	Intron 1 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF511	ENST00000361518.10	c.175C>G	p.Leu59Val	missense_variant	Exon 2 of 6	1	NM_145806.4	ENSP00000355251.5
ZNF511-PRAP1	ENST00000368554.8	c.1C>G	p.Leu1Val	missense_variant	Exon 1 of 8	2		ENSP00000357542.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.175C>G (p.L59V) alteration is located in exon 2 (coding exon 2) of the ZNF511 gene. This alteration results from a C to G substitution at nucleotide position 175, causing the leucine (L) at amino acid position 59 to be replaced by a valine (V). 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	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.025	D;D
Polyphen		0.99	D;.
Vest4		0.50
MutPred		0.65		Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);
MVP		0.030
MPC		1.0
ClinPred		0.91	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.23

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: chr10-135122915;