rs147218077

Variant names:

• chr10-133309421-A-C
• rs147218077
• NM_145806.4:c.185A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-133309421-A-C
• chr10-133309421-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_145806.4(ZNF511):​c.185A>C​(p.Gln62Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000287 in 1,612,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q62H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: ZNF511 NM_145806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32
• Publications: 5 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 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892

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.185A>C	p.Gln62Pro	missense	Exon 2 of 6	NP_665805.2
	ZNF511-PRAP1	NM_001396060.1		c.185A>C	p.Gln62Pro	missense	Exon 2 of 9	NP_001382989.1
	ZNF511	NR_130127.2		n.215A>C		non_coding_transcript_exon	Exon 2 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF511	ENST00000361518.10	TSL:1 MANE Select	c.185A>C	p.Gln62Pro	missense	Exon 2 of 6	ENSP00000355251.5	Q8NB15-2
	ZNF511-PRAP1	ENST00000368554.8	TSL:2	c.11A>C	p.Gln4Pro	missense	Exon 1 of 8	ENSP00000357542.5	H7BY64
	ZNF511	ENST00000855627.1		c.185A>C	p.Gln62Pro	missense	Exon 2 of 6	ENSP00000525686.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152204 Hom.: 0 Cov.: 33

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000131 AC: 32 AN: 245166 AF XY: 0.0000974

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000302 AC: 441 AN: 1460174 Hom.: 0 Cov.: 32 AF XY: 0.000284 AC XY: 206 AN XY: 726346

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.000179 AC: 8 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52234

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5736

European-Non Finnish (NFE) AF: 0.000360 AC: 400 AN: 1111720

Other (OTH) AF: 0.000481 AC: 29 AN: 60338

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74492

African (AFR) AF: 0.0000240 AC: 1 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000263 Hom.: 0

Bravo AF: 0.000174

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000149 AC: 18

EpiCase AF: 0.000109

EpiControl AF: 0.000178

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	Pathogenic	0.70
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.0016
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.55	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.76
MVP		0.67
MPC		1.2
ClinPred		0.52	D
GERP RS		-0.60
PromoterAI		0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.73
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147218077; hg19: chr10-135122925;