NM_145806.4:c.103C>T

Variant names:

• chr10-133309046-C-T
• rs1275603255
• NM_145806.4:c.103C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145806.4(ZNF511):​c.103C>T​(p.Arg35Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000889 in 1,124,730 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
• Consequence: ZNF511 NM_145806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.233
• Publications: 1 publications found

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]

TUBGCP2 Gene-Disease associations (from GenCC):

• pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12565005).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145806.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF511	NM_145806.4	MANE Select	c.103C>T	p.Arg35Cys	missense	Exon 1 of 6	NP_665805.2
	ZNF511-PRAP1	NM_001396060.1		c.103C>T	p.Arg35Cys	missense	Exon 1 of 9	NP_001382989.1
	ZNF511	NR_130127.2		n.133C>T		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF511	ENST00000361518.10	TSL:1 MANE Select	c.103C>T	p.Arg35Cys	missense	Exon 1 of 6	ENSP00000355251.5	Q8NB15-2
	ZNF511	ENST00000855627.1		c.103C>T	p.Arg35Cys	missense	Exon 1 of 6	ENSP00000525686.1
	ZNF511	ENST00000359035.4	TSL:2	c.103C>T	p.Arg35Cys	missense	Exon 1 of 5	ENSP00000351929.3	Q8NB15-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 21096 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.89e-7 AC: 1 AN: 1124730 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 534158

African (AFR) AF: 0.00 AC: 0 AN: 23368

American (AMR) AF: 0.00 AC: 0 AN: 9006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14744

East Asian (EAS) AF: 0.00 AC: 0 AN: 27050

South Asian (SAS) AF: 0.00 AC: 0 AN: 26498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3500

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 938208

Other (OTH) AF: 0.00 AC: 0 AN: 45304

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.23
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.050
Sift	Benign	0.082	T
Sift4G	Benign	0.083	T
Polyphen		0.027	B
Vest4		0.056
MutPred		0.41		Gain of helix (P = 0.0078)
MVP		0.067
MPC		0.50
ClinPred		0.29	T
GERP RS		0.90
PromoterAI		-0.046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.35
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1275603255; hg19: chr10-135122550;