chr2-27615249-C-T

Variant names:

• chr2-27615249-C-T
• NM_032434.4:c.1213C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032434.4(ZNF512):​c.1213C>T​(p.Arg405Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000483 in 1,450,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZNF512 NM_032434.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95
• Publications: 0 publications found

Genes affected

ZNF512 (HGNC:29380): (zinc finger protein 512) This gene encodes a protein containing four putative zinc finger motifs. Zinc finger motifs may bind to proteins or nucleic acids. Zinc finger-containing proteins are involved in a variety of processes, including regulation of transcription. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Sep 2012]

ENSG00000259080 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28858978).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032434.4. 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
	ZNF512	NM_032434.4	MANE Select	c.1213C>T	p.Arg405Cys	missense	Exon 11 of 14	NP_115810.2
	ZNF512	NM_001271286.2		c.1126C>T	p.Arg376Cys	missense	Exon 10 of 13	NP_001258215.1	Q96ME7-3
	ZNF512	NM_001271287.2		c.982C>T	p.Arg328Cys	missense	Exon 10 of 13	NP_001258216.1	Q96ME7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF512	ENST00000355467.6	TSL:2 MANE Select	c.1213C>T	p.Arg405Cys	missense	Exon 11 of 14	ENSP00000347648.3	Q96ME7-1
	ZNF512	ENST00000556601.5	TSL:1	c.982C>T	p.Arg328Cys	missense	Exon 10 of 13	ENSP00000451572.2	Q96ME7-2
	ZNF512	ENST00000879762.1		c.1213C>T	p.Arg405Cys	missense	Exon 11 of 14	ENSP00000549821.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000483 AC: 7 AN: 1450044 Hom.: 0 Cov.: 29 AF XY: 0.00000416 AC XY: 3 AN XY: 721362

African (AFR) AF: 0.00 AC: 0 AN: 32966

American (AMR) AF: 0.0000232 AC: 1 AN: 43040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25982

East Asian (EAS) AF: 0.00 AC: 0 AN: 38934

South Asian (SAS) AF: 0.00 AC: 0 AN: 83962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1106154

Other (OTH) AF: 0.0000167 AC: 1 AN: 59994

GnomAD4 genome Cov.: 33

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	0.10
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.087	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.27
Sift	Benign	0.035	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.47		Loss of MoRF binding (P = 0.0051)
MVP		0.093
MPC		1.6
ClinPred		0.92	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.55
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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

hg19: chr2-27838116; COSMIC: COSV62675818; COSMIC: COSV62675818;